1022688401@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Molecular</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">immune</tok> <tok cat="NN">response</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1022688402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Cytokine</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">immune</tok> <tok cat="NN">system</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">important</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">immune</tok> <tok cat="NN">response</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1022688403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">On</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">first</tok> <tok cat="NN">encounter</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">antigen</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="JJ">naive</tok> <tok cat="JJ">CD4+</tok> <tok cat="NN">T</tok> <tok cat="NN">helper</tok> <tok cat="LRB">(</tok><tok cat="NN">Th</tok><tok cat="RRB">)</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">differentiate</tok> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="JJ">cytokine-producing</tok> <tok cat="NN">effector</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1022688404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="CD">Two</tok> <tok cat="NNS">types</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">effector</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">characterized</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="JJ">distinct</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NNS">profiles</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">described</tok><cons cat="NP" ref="i1" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1022688405@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Th1</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">produce</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IFN-gamma</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Th2</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">produce</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-4</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-5</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-6</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-13</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1022688406@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="JJ">many</tok> <tok cat="JJ">pathological</tok> <tok cat="NNS">situations</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">balance</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Th1</tok> <cons cat="NP" ref="i2" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Th2</tok> <cons cat="NP" ref="i2" null="RNR"></cons></cons><cons cat="NP" id="i2"><tok cat="JJ">immune</tok> <tok cat="NNS">responses</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">determines</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">outcome</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">diverse</tok> <tok cat="RB">immunologically</tok> <tok cat="VBN">mediated</tok> <tok cat="JJ">clinical</tok> <tok cat="NNS">syndromes</tok></cons> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">infectious</tok><cons cat="NP" ref="i3" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">autoimmune</tok><cons cat="NP" ref="i3" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">allergic</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons></cons><cons cat="NP" id="i3"><tok cat="NNS">diseases</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1022688407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">basis</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">tissue-specific</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">Th1/Th2-like</tok> <tok cat="NNS">cytokines</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">remained</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">elusive</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1022688408@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">review</tok></cons></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">evaluate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">possible</tok> <tok cat="FW">in</tok> <tok cat="FW">vivo</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">different</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NNS">mechanisms</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">immune</tok> <tok cat="NN">response</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1022800801@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="RB">evolutionarily</tok> <tok cat="VBN">conserved</tok> <tok cat="NN">sequence</tok> <tok cat="RB">upstream</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">human</tok> <tok cat="NN">Ig</tok> <tok cat="JJ">heavy</tok> <tok cat="NN">chain</tok> <tok cat="NN">S</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="NN">region</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">inducible</tok> <tok cat="NN">promoter</tok></cons><tok cat="COLON">:</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">synergistic</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CD40</tok> <tok cat="NN">ligand</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-4</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><tok cat="JJ">cooperative</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT-6</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons></cons><cons cat="NP" id="i1"><tok cat="NN">binding</tok> <tok cat="NNS">sites</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1022800802@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Germline</tok> <tok cat="NN">C</tok> <tok cat="NN">gamma</tok> <tok cat="NN">gene</tok> <tok cat="NN">transcription</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">crucial</tok> <tok cat="NN">event</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">process</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" id="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">leads</tok> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">switch</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NN">recombination</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">IgG</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">human</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">poorly</tok></cons> <cons cat="VP"><tok cat="VBN">understood</tok><cons cat="NP" ref="i4" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1022800803@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">took</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">advantage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">our</tok> <tok cat="JJ">monoclonal</tok> <tok cat="NN">model</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">germinal</tok> <tok cat="NN">center</tok> <tok cat="NN">B</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">IgM+</tok> <tok cat="JJ">IgD+</tok> <tok cat="NN">CL-01</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">define</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">I</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="RB">evolutionarily</tok> <tok cat="VBN">conserved</tok> <tok cat="NN">sequence</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">ECS</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">germline</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">human</tok> <tok cat="NN">C</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@47@@oe@16-12-2010 1022800804@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="NN">I</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok></cons> <cons cat="NP"><tok cat="NN">ECS</tok></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">lies</tok> <cons cat="ADVP"><tok cat="RB">upstream</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">major</tok> <tok cat="NN">I</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="NN">transcription</tok> <tok cat="NN">initiation</tok> <tok cat="NN">site</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">displays</tok> <cons cat="NP"><cons cat="NP"><cons cat="QP"><tok cat="JJR">more</tok> <tok cat="IN">than</tok> <tok cat="CD">90</tok><tok cat="NN">%</tok></cons> <tok cat="NN">identity</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">corresponding</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">I</tok> <tok cat="NN">gamma</tok> <tok cat="CD">1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">I</tok> <tok cat="NN">gamma</tok> <tok cat="CD">2</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">I</tok> <tok cat="NN">gamma</tok> <tok cat="CD">4</tok></cons></cons> <tok cat="NNS">regions</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1022800805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" id="i5"><tok cat="NN">Reporter</tok> <tok cat="NN">luciferase</tok> <tok cat="NN">gene</tok> <tok cat="NNS">vectors</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">containing</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">human</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="NN">ECS</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">transfect</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CL-01</tok> <tok cat="NNS">cells</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" id="i7" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">undergo</tok> <cons cat="NP"><tok cat="NN">Smu</tok><tok cat="TO">--></tok><tok cat="NN">S</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="NN">DNA</tok> <tok cat="NN">recombination</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">engagement</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CD40</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">CD40</tok> <tok cat="NN">ligand</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">CD40L</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">exposure</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">IL-4</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@46@@oe@16-12-2010 1022800806@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="VBN">transfected</tok> <tok cat="NN">CL-01</tok> <tok cat="NNS">cells</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">CD40:CD40L</tok> <tok cat="NN">engagement</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">exposure</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">IL-4</tok></cons></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">synergistically</tok></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="JJ">ECS-dependent</tok> <tok cat="NN">luciferase</tok> <tok cat="NN">reporter</tok> <tok cat="NN">gene</tok> <tok cat="NN">activation</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1022800807@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="VBN">Targeted</tok> <tok cat="JJ">mutational</tok> <tok cat="NN">analysis</tok></cons> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">a</tok> <tok cat="JJ">tandem</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B/Rel</tok> <tok cat="NN">binding</tok> <tok cat="NN">motif</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">critical</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="NN">ECS</tok> <tok cat="NN">responsiveness</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">CD40L</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-4</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="DT">a</tok> <tok cat="JJ">STAT-6-binding</tok> <tok cat="NN">site</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">additionally</tok></cons> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">IL-4</tok> <tok cat="NN">inducibility</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1022800808@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Electrophoretic</tok> <tok cat="NN">mobility</tok> <tok cat="NN">shift</tok> <tok cat="NNS">assays</tok></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i9" role="SBJ"><cons cat="NP"><tok cat="NN">p50/p65/c-Rel</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT-6</tok></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">effectively</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><cons cat="NP"><tok cat="NN">CD40L</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-4</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">respectively</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">bind</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">specific</tok> <tok cat="NN">DNA</tok> <tok cat="NNS">motifs</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ECS</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1022800809@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <cons cat="ADJP"><tok cat="RB">partially</tok> <tok cat="VBG">overlapping</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CD40L</tok> <cons cat="NP" ref="i10" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-4</tok> <cons cat="NP" ref="i10" null="RNR"></cons></cons><cons cat="NP" id="i10"><tok cat="JJ">responsive</tok> <tok cat="NNS">elements</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">functionally</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">cooperative</tok></cons> <cons cat="SBAR"><tok cat="IN">as</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">disruption</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">one</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="PRP">them</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">prevents</tok> <cons cat="NP"><tok cat="JJ">synergistic</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1022800810@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Thus</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="NN">ECS</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP" id="i11"><tok cat="DT">an</tok> <tok cat="JJ">inducible</tok> <tok cat="NN">promoter</tok></cons> <cons cat="VP"><tok cat="VBG">containing</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cis</tok> <tok cat="NNS">elements</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i12"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i12" role="SBJ" null="T"></cons><cons cat="ADVP"><tok cat="RB">critically</tok></cons> <cons cat="VP"><tok cat="VBP">mediate</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CD40L</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">IL-4-triggered</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activation</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">human</tok> <tok cat="NN">C</tok> <tok cat="NN">gamma</tok> <tok cat="CD">3</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1022801101@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">HLA</tok> <tok cat="NN">class</tok> <tok cat="JJ">I-mediated</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">proliferation</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">involves</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">cyclin</tok> <tok cat="JJ">E-mediated</tok> <tok cat="NN">inactivation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Rb</tok> <tok cat="NN">function</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">E2F</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1022801102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="JJ">Chronic</tok> <tok cat="NN">rejection</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">transplanted</tok> <tok cat="NNS">organs</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">manifested</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">atherosclerosis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">blood</tok> <tok cat="NNS">vessels</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">allograft</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1022801103@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NN">HLA</tok> <tok cat="NN">class</tok> <tok cat="CD">I</tok> <tok cat="NNS">Ags</tok></cons> <tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">implicated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">play</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">major</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">process</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">since</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="VBG">signaling</tok></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><tok cat="NN">HLA</tok> <tok cat="NN">class</tok> <tok cat="CD">I</tok> <tok cat="NNS">molecules</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">proliferation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">aortic</tok> <tok cat="NN">endothelial</tok></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="NP"><tok cat="JJ">smooth</tok> <tok cat="NN">muscle</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1022801104@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">HLA</tok> <tok cat="NN">class</tok> <tok cat="JJ">I-mediated</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">proliferation</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">correlates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">inactivation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Rb</tok> <tok cat="NN">protein</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok> <tok cat="NN">Jurkat</tok></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">aortic</tok> <tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1022801105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">HLA</tok> <tok cat="NN">class</tok> <tok cat="JJ">I-mediated</tok> <tok cat="NN">inactivation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Rb</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">specifically</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="VBG">neutralizing</tok> <tok cat="NNS">Abs</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">basic</tok> <tok cat="NN">fibroblast</tok> <tok cat="NN">growth</tok> <tok cat="NN">factor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">bFGF</tok></cons><tok cat="RRB">)</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">suggesting</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">FGF</tok> <tok cat="NNS">receptors</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">signaling</tok> <tok cat="NN">process</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1022801106@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="VBG">Signaling</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="NN">HLA</tok> <tok cat="NN">class</tok> <tok cat="CD">I</tok> <tok cat="NNS">molecules</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><tok cat="NN">cyclin</tok> <tok cat="JJ">E-associated</tok> <tok cat="NN">kinase</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="CD">4</tok> <tok cat="NN">h</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">quiescent</tok> <tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">appeared</tok> <cons cat="S" role="PRD"><cons cat="NP" ref="i4" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">mediate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">inactivation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Rb</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1022801107@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="NN">cdk2</tok> <tok cat="NN">inhibitor</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">Olomoucine</tok></cons><tok cat="COMMA">,</tok> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dominant-negative</tok> <tok cat="NN">cdk2</tok> <tok cat="NN">construct</tok></cons></cons> <cons cat="VP"><tok cat="VBD">prevented</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">HLA</tok> <tok cat="NN">class</tok> <tok cat="JJ">I-mediated</tok> <tok cat="NN">inactivation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Rb</tok></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><tok cat="JJ">dominant-negative</tok> <cons cat="NP"><tok cat="NN">cdk4</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cdk6</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><cons cat="NP" id="i5"><tok cat="NNS">constructs</tok></cons></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><tok cat="DT">no</tok> <tok cat="NN">effect</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1022801108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="EX">there</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">no</tok> <tok cat="NN">increase</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cyclin</tok> <tok cat="JJ">D-associated</tok> <tok cat="NN">kinase</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><tok cat="NN">HLA</tok> <tok cat="NN">class</tok> <tok cat="CD">I</tok> <tok cat="NN">ligation</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">suggesting</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">cyclin</tok> <tok cat="JJ">E-dependent</tok> <tok cat="NN">kinase</tok> <tok cat="NN">activity</tok></cons> <cons cat="VP"><tok cat="VBZ">mediates</tok> <cons cat="NP"><tok cat="NN">Rb</tok> <tok cat="NN">inactivation</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">leading</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">E2F</tok> <tok cat="NN">activation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">proliferation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1022802601@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Thrombin-induced</tok> <tok cat="NN">p65</tok> <tok cat="NN">homodimer</tok></cons> <cons cat="VP"><tok cat="NN">binding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">downstream</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">site</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">mediates</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NN">ICAM-1</tok> <tok cat="NN">expression</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">neutrophil</tok> <tok cat="NN">adhesion</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1022802602@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">investigated</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i1"><tok cat="IN">by</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">proinflammatory</tok> <tok cat="NN">mediator</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">thrombin</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">released</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">intravascular</tok> <tok cat="NN">coagulation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">tissue</tok> <tok cat="NN">injury</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">ICAM-1</tok> <tok cat="LRB">(</tok><tok cat="NN">CD54</tok><tok cat="RRB">)</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons></cons><cons cat="PP" ref="i1" null="T"></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1022802603@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Stimulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HUVEC</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">thrombin</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">resulted</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="NN">dose-</tok> <cons cat="ADJP" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">time-dependent</tok></cons></cons> <tok cat="NNS">increases</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">ICAM-1</tok> <tok cat="NN">mRNA</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">surface</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">ICAM-1-dependent</tok> <tok cat="JJ">endothelial</tok> <tok cat="NN">adhesivity</tok></cons> <cons cat="PP"><tok cat="IN">toward</tok> <cons cat="NP"><tok cat="JJ">polymorphonuclear</tok> <tok cat="NNS">leukocytes</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1022802604@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Transient</tok> <tok cat="NN">transfection</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">ICAM-1</tok> <tok cat="NN">promoter</tok> <tok cat="NN">luciferase</tok> <tok cat="NN">reporter</tok> <tok cat="NN">gene</tok></cons> <tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">ICAM-1LUC</tok></cons><tok cat="RRB">)</tok></cons> <tok cat="NNS">constructs</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">indicated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">deletion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">upstream</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">site</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="CD">-533</tok> <tok cat="NNS">bases</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">translation</tok> <tok cat="NN">start</tok> <tok cat="NN">site</tok></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">no</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">thrombin</tok> <tok cat="NN">responsiveness</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">mutation/deletion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">downstream</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">site</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="CD">-223</tok> <tok cat="NNS">bases</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">translation</tok> <tok cat="NN">start</tok> <tok cat="NN">site</tok></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">prevented</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">ICAM-1</tok> <tok cat="NN">promoter</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">indicating</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="JJ">downstream</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">site</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">critical</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">thrombin</tok> <tok cat="NN">inducibility</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@74@@oe@16-12-2010 1022802605@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NF-kappa</tok> <tok cat="JJ">B-directed</tok> <tok cat="NN">luciferase</tok> <tok cat="NN">activity</tok></cons> <cons cat="VP"><tok cat="VBD">increased</tok> <cons cat="NP"><tok cat="RB">approximately</tok> <tok cat="RB">3-fold</tok></cons> <cons cat="SBAR"><cons cat="WHADVP" id="i2" adv="TMP"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">transfected</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">plasmid</tok> <tok cat="NN">pNF-kappa</tok> <tok cat="NN">BLUC</tok></cons> <cons cat="VP"><tok cat="VBG">containing</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="CD">five</tok> <tok cat="NNS">copies</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">consensus</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">site</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">linked</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">minimal</tok> <tok cat="NN">adenovirus</tok> <tok cat="NN">E1B</tok> <tok cat="JJ">promoter-luciferase</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">exposed</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">thrombin</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">indicating</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">essential</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">thrombin</tok> <tok cat="NN">response</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@48@@oe@16-12-2010 1022802606@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Gel</tok> <tok cat="NN">supershift</tok> <tok cat="NNS">assays</tok></cons> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">thrombin</tok></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">Bp65</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">Rel</tok> <tok cat="NN">A</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">downstream</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">site</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ICAM-1</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1022802607@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Thrombin</tok> <tok cat="NN">receptor</tok> <tok cat="NN">activation</tok> <tok cat="NN">peptide</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">14-amino-acid</tok> <tok cat="NN">peptide</tok></cons></cons> <cons cat="VP"><tok cat="VBG">representing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">new</tok> <tok cat="NN">NH2</tok> <tok cat="NN">terminus</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="RB">proteolytically</tok> <tok cat="VBN">activated</tok></cons> <tok cat="NN">receptor-1</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBD">mimicked</tok> <cons cat="NP" id="i5"><tok cat="NN">thrombin</tok><tok cat="POS">'s</tok> <tok cat="NN">action</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">inducing</tok> <cons cat="NP"><tok cat="NN">ICAM-1</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1022802608@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">thrombin</tok></cons> <cons cat="VP"><tok cat="VBZ">activates</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NN">ICAM-1</tok> <tok cat="NN">expression</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">polymorphonuclear</tok> <tok cat="NN">leukocyte</tok> <tok cat="NN">adhesion</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">Bp65</tok></cons> <cons cat="VP"><tok cat="VBG">binding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">downstream</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">site</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">ICAM-1</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="RB">proteolytically</tok> <tok cat="VBN">activated</tok></cons> <tok cat="JJ">receptor-1</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1022813301@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="VBN">Increased</tok> <tok cat="NN">glucocorticoid</tok> <tok cat="NN">receptor</tok> <tok cat="NN">beta</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">airway</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">glucocorticoid-insensitive</tok> <tok cat="NN">asthma</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1022813302@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Glucocorticoid</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">GC</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="JJ">-insensitive</tok> <tok cat="NN">asthma</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">challenging</tok> <tok cat="JJ">clinical</tok> <tok cat="NN">problem</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" id="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">life-threatening</tok> <tok cat="NN">disease</tok> <tok cat="NN">progression</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1022813303@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">basis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">GC</tok> <tok cat="NN">insensitivity</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="JJ">unknown</tok><cons cat="NP" ref="i3" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@9@@oe@16-12-2010 1022813304@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Alternative</tok> <tok cat="NN">splicing</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">GC</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">GCR</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">pre-mRNA</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><tok cat="VBZ">generates</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">second</tok> <tok cat="NN">GCR</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">termed</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="NP" role="PRD"><tok cat="NN">GCRbeta</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">bind</tok> <cons cat="NP"><tok cat="NN">GC</tok></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBZ">antagonizes</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transactivating</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">classic</tok> <tok cat="NN">GCR</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1022813305@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Thus</tok></cons> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">GCRbeta</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">could</tok> <cons cat="VP"><tok cat="VB">account</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">glucocorticoid</tok> <tok cat="NN">insensitivity</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1022813306@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" id="i5" role="SBJ"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Bronchoalveolar</tok> <tok cat="NN">lavage</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">BAL</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NNS">cells</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">PBMC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">examined</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">GCRbeta</tok> <tok cat="NN">immunoreactivity</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">GCRbeta-specific</tok> <tok cat="NN">antibody</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="JJ">immunohistochemical</tok> <tok cat="NN">staining</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1022813307@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="NN">Cell</tok> <tok cat="NN">localization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">GCRbeta</tok> <tok cat="NN">expression</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">performed</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">double</tok> <tok cat="JJ">immunostaining</tok> <tok cat="NN">technique</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1022813308@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">Patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">GC-insensitive</tok> <tok cat="NN">asthma</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">expressed</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <cons cat="ADJP"><tok cat="RB">significantly</tok> <tok cat="JJR">higher</tok></cons> <tok cat="NN">number</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">GCRbeta-immunoreactive</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">BAL</tok> <cons cat="NP" ref="i7" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="JJ">peripheral</tok> <cons cat="NP" ref="i7" null="RNR"></cons></cons></cons><cons cat="NP" id="i7"><tok cat="NN">blood</tok></cons></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">GC-sensitive</tok> <tok cat="NNS">asthmatics</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1022813309@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">GCRbeta</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">GC-insensitive</tok> <tok cat="NN">asthma</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">particularly</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">high</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">airway</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i8"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i8" id="i9" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">thought</tok> <cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">play</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">major</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">pathogenesis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">asthma</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1022813310@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBD">examined</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">GCRbeta</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">specimens</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">airways</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">bronchitis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1022813311@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">bronchitis</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">few</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">GCRbeta-positive</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">their</tok> <tok cat="NNS">numbers</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">differ</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1022813312@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">conclude</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i10" role="SBJ"><tok cat="JJ">GC-insensitive</tok> <tok cat="NN">asthma</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">GCRbeta</tok> <tok cat="IN">in</tok> <tok cat="NN">airway</tok></cons> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1022923101@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Fas</tok> <tok cat="NN">ligand</tok> <tok cat="NN">expression</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">death</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">apoptosis-linked</tok> <tok cat="NN">gene</tok> <tok cat="CD">4</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1022923102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="VBN">Programmed</tok> <tok cat="NN">cell</tok> <tok cat="NN">death</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">process</tok></cons> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">normal</tok> <tok cat="NN">development</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">organism</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1022923103@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="CD">One</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP"><tok cat="JJS">best</tok> <tok cat="VBN">understood</tok></cons> <tok cat="JJ">apoptotic</tok> <tok cat="NNS">pathways</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">occurs</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">Fas/Fas</tok> <tok cat="NN">ligand</tok> <tok cat="LRB">(</tok><tok cat="NN">FasL</tok><tok cat="RRB">)</tok> <tok cat="NN">interaction</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1022923104@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP" adv="TMP"><tok cat="IN">During</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">studies</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">apoptosis</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">T</tok> <tok cat="NN">cell-receptor</tok> <tok cat="NN">engagement</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">identified</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">ALG-4F</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="VBN">truncated</tok> <tok cat="NN">transcript</tok></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">prevents</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="JJ">cell-receptor-induced</tok> <tok cat="NN">FasL</tok> <tok cat="NN">upregulation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">death</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1022923105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Overexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">full-length</tok> <tok cat="NN">ALG-4</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">FasL</tok></cons></cons></cons> <tok cat="CC">and</tok><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">consequently</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1022923106@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">ALG-4</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" syn="COOD" role="PRD"><cons cat="ADJP"><tok cat="JJ">necessary</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">sufficient</tok></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">FasL</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1022923107@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Fas/FasL</tok> <tok cat="NN">interaction</tok></cons> <cons cat="VP"><tok cat="VBZ">initiates</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">death</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">many</tok> <tok cat="JJ">other</tok> <tok cat="NNS">systems</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">its</tok> <tok cat="NN">dysregulation</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">mechanism</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i4"><tok cat="IN">by</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">several</tok> <tok cat="JJ">pathologic</tok> <tok cat="NNS">conditions</tok></cons> <cons cat="VP"><tok cat="VBP">arise</tok><cons cat="PP" ref="i4" null="T"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1022923108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" role="SBJ"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">Understanding</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">molecular</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">FasL</tok> <tok cat="NN">regulation</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">could</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADVP"><tok cat="RB">very</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">useful</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">elucidating</tok> <cons cat="SBAR"><cons cat="WHADVP" id="i5"><tok cat="WRB">how</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">diseases</tok></cons> <cons cat="VP"><tok cat="VBP">develop</tok> <cons cat="ADVP" ref="i5" null="T"></cons></cons></cons></cons></cons></cons></cons><tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">identifying</tok> <cons cat="NP"><tok cat="JJ">potential</tok> <tok cat="JJ">therapeutic</tok> <tok cat="NNS">targets</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1022927501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">High</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">weight</tok> <tok cat="NN">dextran</tok> <tok cat="NN">sulfate</tok></cons> <cons cat="VP"><tok cat="VBZ">increases</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">NF-kappaB-regulated</tok> <tok cat="NN">promoter</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">monocyte-derived</tok> <tok cat="NNS">macrophages</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1022927502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">It</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">sulfated</tok> <tok cat="NNS">polysaccharides</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">mimic</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">action</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">common</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">mitogens</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1022927503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">investigate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">basis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">mitogenic</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">high</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">weight</tok> <tok cat="NN">dextran</tok> <tok cat="NN">sulfate</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">HMDS</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><tok cat="JJ">monocyte-derived</tok> <tok cat="NNS">macrophages</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">transfected</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">recombinant</tok> <tok cat="NN">plasmid</tok></cons> <cons cat="VP"><tok cat="VBG">containing</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">chloramphenicol</tok> <tok cat="NN">acetyl</tok> <tok cat="NN">transferase</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">CAT</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">reporter</tok> <tok cat="NN">gene</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">under</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">HIV-1</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">long</tok> <tok cat="JJ">terminal</tok> <tok cat="NN">repeat</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">LTR</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">promoter</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" id="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">regulated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@57@@oe@16-12-2010 1022927504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">observed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">HMDS</tok></cons><tok cat="COMMA">,</tok> <cons cat="ADJP"><tok cat="JJ">similar</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">bacterial</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">lipopolysaccharide</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">LPS</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">increases</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CAT</tok> <tok cat="NN">reporter</tok> <tok cat="NN">gene</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">suggesting</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1022927505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">correlated</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">increased</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">B7.1</tok> <tok cat="NNS">molecules</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1022927506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">It</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">postulated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">this</tok> <tok cat="JJ">NF-kappaB-regulated</tok> <tok cat="NN">promoter</tok></cons> <cons cat="VP"><tok cat="MD">might</tok> <cons cat="VP"><tok cat="VB">play</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">accessory</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="ADVP"><cons cat="ADVP"><tok cat="RB">as</tok> <tok cat="RB">well</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">rate</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">replication</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">monocyte-derived</tok> <tok cat="NNS">macrophages</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1022932401@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">Differences</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-2R</tok> <tok cat="JJ">associated</tok> <tok cat="NN">JAK/STAT</tok> <tok cat="NNS">proteins</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP" syn="COOD"><tok cat="JJ">HTLV-I(+)</tok><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">IL-2-independent</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">IL-2-dependent</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">uncultured</tok> <tok cat="JJ">leukemic</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">adult</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">lymphoma/leukemia</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1022932402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">determine</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok> <tok cat="NN">status</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">IL-2R-associated</tok> <tok cat="LRB">(</tok><tok cat="NN">Jak/STAT</tok><tok cat="RRB">)</tok> <tok cat="NN">pathway</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">HTLV-I</tok> <tok cat="JJ">infected</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">examined</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Jak3</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">STAT3</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">several</tok> <tok cat="JJ">HTLV-I(+)</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">lines</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">uncultured</tok> <tok cat="JJ">leukemic</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">isolated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">adult</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">lymphoma/leukemia</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">ATLL</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@50@@oe@16-12-2010 1022932403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="JJ">Constitutive</tok> <tok cat="JJ">basal</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Jak3</tok></cons> <tok cat="CC">and</tok><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">usually</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">STAT3</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">all</tok> <tok cat="CD">four</tok> <tok cat="JJ">IL-2-independent</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons> <cons cat="VP"><tok cat="VBN">tested</tok><cons cat="NP" null="NONE"></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">none</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="CD">three</tok> <tok cat="JJ">IL-2-dependent</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1022932404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Similarly</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="EX">there</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="NP" role="PRD"><cons cat="NP"><cons cat="NP"><tok cat="DT">no</tok> <tok cat="JJ">detectable</tok> <tok cat="JJ">basal</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Jak3</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">leukemic</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">ATLL</tok> <tok cat="NNS">patients</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">0/8</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="CD">0/3</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">respectively</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1022932405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">stimulation</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">IL-2</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">resulted</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Jak3</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="JJ">leukemic</tok> <tok cat="NN">ATLL</tok> <tok cat="NNS">cells</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">IL-2-dependent</tok> <tok cat="NNS">lines</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1022932406@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">SHP-1</tok> <tok cat="NN">phosphatase</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">negative</tok> <tok cat="NN">regulator</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NN">receptor</tok> <tok cat="NN">signaling</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="VBN">lost</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJS">most</tok> <tok cat="NN">IL-2</tok> <tok cat="JJ">independent</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">3/4</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">leukemic</tok> <tok cat="NN">ATLL</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">0/3</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1022932407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP" role="PRD"><tok cat="RB">Finally</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">HTLV-I(+)</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">lines</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">313</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">control</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">HTLV-I(-)</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">lines</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">resistant</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">rapamycin</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">novel</tok> <tok cat="NN">analog</tok> <tok cat="NN">RAD</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1022932408@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">conclude</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S" syn="COOD"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">1</tok><tok cat="RRB">)</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">HTLV-I</tok> <tok cat="NN">infection</tok></cons> <cons cat="PP"><tok cat="FW">per</tok> <cons cat="NP"><tok cat="FW">se</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">result</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">constitutive</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">Jak3</tok><cons cat="NP" ref="i6" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">STAT3</tok><cons cat="NP" ref="i6" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><cons cat="NP" id="i6"><tok cat="NNS">proteins</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">2</tok><tok cat="RRB">)</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">malignant</tok> <tok cat="NN">transformation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="ADVP"><tok cat="IN">at</tok> <tok cat="JJS">least</tok></cons> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="NNS">cases</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">ATLL</tok></cons></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">require</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">constitutive</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">require</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">IL-2-induced</tok><tok cat="COMMA">,</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-2R</tok> <tok cat="NN">Jak/STAT</tok> <tok cat="NN">pathway</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <tok cat="CC">and</tok> <cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">3</tok><tok cat="RRB">)</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="EX">there</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">major</tok> <tok cat="NNS">differences</tok></cons> <cons cat="SBAR" ref="i7" null="ICH"></cons></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NN">immortalization</tok> <tok cat="NN">mechanism</tok><cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">s</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="SBAR" id="i7"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" id="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">appear</tok> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">involve</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">SHP-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">target</tok> <tok cat="NNS">molecules</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">rapamycin</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">RAD</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@85@@oe@16-12-2010 1022981501@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">CTLA-4-Mediated</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">early</tok> <tok cat="NNS">events</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">proliferation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@10@@oe@16-12-2010 1022981502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">CTLA-4</tok> <tok cat="NN">engagement</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NNS">mAbs</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok><tok cat="COMMA">,</tok> <cons cat="PRN"><cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="NP" role="SBJ"><tok cat="NN">CD28</tok></cons> <cons cat="VP"><tok cat="VBZ">enhances</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">production</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">proliferation</tok></cons></cons> <cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1022981503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i1" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">analyzed</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">CTLA-4-mediated</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">naive</tok> <tok cat="JJ">CD4+</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="NN">Ab</tok> <tok cat="NN">cross-linking</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1022981504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NN">CTLA-4</tok> <tok cat="NN">ligation</tok></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><tok cat="JJ">CD3/CD28-induced</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">mRNA</tok> <tok cat="NN">accumulation</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">inhibiting</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">transcription</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" id="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">appears</tok> <cons cat="S"><cons cat="NP" ref="i4" id="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">part</tok></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">decreasing</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-AT</tok> <tok cat="NN">accumulation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">nuclei</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1022981505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i6" role="SBJ"><tok cat="NN">CTLA-4</tok> <tok cat="NN">ligation</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">appear</tok> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">CD28-mediated</tok> <tok cat="NN">stabilization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">mRNA</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1022981506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Further</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7" role="SBJ"><tok cat="NN">CTLA-4</tok> <tok cat="NN">engagement</tok></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><tok cat="NN">progression</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cell</tok> <tok cat="NN">cycle</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">inhibiting</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">cyclin</tok> <tok cat="NN">D3</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">cyclin-dependent</tok> <tok cat="NN">kinase</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">cdk</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="CD">4</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cdk6</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="SBAR" adv="TMP"><cons cat="WHADVP"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" id="i9" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">stimulated</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">anti-CD3/CD28</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">anti-CD3</tok></cons> <cons cat="ADJP"><tok cat="RB">alone</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1022981507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">CTLA-4</tok> <tok cat="NN">signaling</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><tok cat="NNS">events</tok></cons> <cons cat="PP"><cons cat="ADVP"><tok cat="RB">early</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok></cons></cons></cons> <cons cat="PP" syn="COOD"><tok cat="CC">both</tok> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">transcription</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">level</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">IL-2-independent</tok> <tok cat="NNS">events</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cell</tok> <tok cat="NN">cycle</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="ADVP"><tok cat="RB">simply</tok></cons> <cons cat="VP"><tok cat="VB">oppose</tok> <cons cat="NP"><tok cat="JJ">CD28-mediated</tok> <tok cat="NN">costimulation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1022982001@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Fibroblast</tok> <tok cat="NN">growth</tok> <tok cat="NN">factor-1</tok> <tok cat="LRB">(</tok><tok cat="NN">FGF-1</tok><tok cat="RRB">)</tok></cons> <tok cat="VBZ">enhances</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">production</tok> <tok cat="CC">and</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok> <tok cat="IN">of</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="IN">in</tok> <tok cat="NN">FGF</tok> <tok cat="JJ">receptor-bearing</tok> <tok cat="NN">Jurkat</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1022982002@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="NN">Fibroblast</tok> <tok cat="NN">growth</tok> <tok cat="NNS">factors</tok> <tok cat="LRB">(</tok><tok cat="NNS">FGFs</tok><tok cat="RRB">)</tok> <tok cat="VBP">are</tok> <tok cat="JJ">heparin-binding</tok> <tok cat="NNS">proteins</tok> <tok cat="JJ">crucial</tok> <tok cat="TO">to</tok> <tok cat="NN">embryogenesis</tok><tok cat="COMMA">,</tok> <tok cat="NN">angiogenesis</tok><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <tok cat="NN">wound</tok> <tok cat="NN">healing</tok><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1022982003@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="NN">FGF-1</tok> <tok cat="VBZ">is</tok> <tok cat="RB">abundantly</tok> <tok cat="VBN">expressed</tok> <tok cat="IN">in</tok> <tok cat="DT">the</tok> <tok cat="NN">synovium</tok> <tok cat="IN">in</tok> <tok cat="NN">rheumatoid</tok> <tok cat="NN">arthritis</tok> <tok cat="CC">and</tok> <tok cat="IN">in</tok> <tok cat="VBG">rejecting</tok> <tok cat="NNS">allografts</tok><tok cat="COMMA">,</tok> <tok cat="NNS">sites</tok> <tok cat="IN">of</tok> <tok cat="JJ">chronic</tok> <tok cat="JJ">immune-mediated</tok> <tok cat="NN">inflammation</tok><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1022982004@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="DT">The</tok> <tok cat="NN">frequency</tok> <tok cat="IN">of</tok> <tok cat="JJ">FGF-1-responsive</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok> <tok cat="VBZ">is</tok> <tok cat="VBN">increased</tok> <tok cat="IN">in</tok> <tok cat="DT">the</tok> <tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="IN">of</tok> <tok cat="DT">these</tok> <tok cat="NNS">disorders</tok><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <tok cat="DT">a</tok> <tok cat="JJ">high</tok> <tok cat="NN">percentage</tok> <tok cat="IN">of</tok> <tok cat="VBG">infiltrating</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok> <tok cat="IN">in</tok> <tok cat="JJ">rheumatoid</tok> <tok cat="NN">arthritis</tok> <tok cat="NN">synovium</tok> <tok cat="VBP">express</tok> <tok cat="NNS">receptors</tok> <tok cat="IN">for</tok> <tok cat="NN">FGF-1</tok><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1022982005@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="TO">To</tok> <tok cat="VB">understand</tok> <tok cat="DT">the</tok> <tok cat="NN">action</tok> <tok cat="IN">of</tok> <tok cat="NN">FGF-1</tok> <tok cat="IN">in</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok><tok cat="COMMA">,</tok> <tok cat="NNS">studies</tok> <tok cat="VBD">were</tok> <tok cat="VBN">initiated</tok> <tok cat="IN">in</tok> <tok cat="NN">Jurkat</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok> <tok cat="WDT">that</tok> <tok cat="VBP">express</tok> <tok cat="DT">the</tok> <tok cat="JJ">signaling</tok> <tok cat="NN">isoform</tok> <tok cat="IN">of</tok> <tok cat="NN">FGF</tok> <tok cat="NN">receptor-1</tok><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1022982006@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="DT">These</tok> <tok cat="NNS">experiments</tok> <tok cat="VBP">show</tok> <tok cat="IN">that</tok> <tok cat="NN">FGF-1</tok> <tok cat="NN">stimulation</tok> <tok cat="IN">of</tok> <tok cat="NN">Jurkat</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok> <tok cat="VBZ">provides</tok> <tok cat="DT">a</tok> <tok cat="JJ">second</tok> <tok cat="NN">signal</tok> <tok cat="WDT">that</tok> <tok cat="VBZ">augments</tok> <tok cat="JJ">TCR-mediated</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">production</tok><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1022982007@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="JJ">Analogous</tok> <tok cat="TO">to</tok> <tok cat="NN">costimulation</tok> <tok cat="IN">via</tok> <tok cat="NN">CD28</tok><tok cat="COMMA">,</tok> <tok cat="DT">this</tok> <tok cat="NN">activity</tok> <tok cat="VBZ">is</tok> <tok cat="VBN">mediated</tok> <tok cat="IN">through</tok> <tok cat="NN">activation</tok> <tok cat="IN">of</tok> <tok cat="NN">Rel/kappaB</tok><tok cat="COMMA">,</tok> <tok cat="DT">a</tok> <tok cat="NN">family</tok> <tok cat="IN">of</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok> <tok cat="VBN">known</tok> <tok cat="TO">to</tok> <tok cat="VB">regulate</tok> <tok cat="NN">IL-2</tok> <tok cat="CC">and</tok> <tok cat="JJ">other</tok> <tok cat="JJ">activation-inducible</tok> <tok cat="NNS">proteins</tok><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1022982008@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="NN">FGF-1</tok> <tok cat="RB">alone</tok> <tok cat="VBZ">induces</tok> <tok cat="JJ">modest</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok> <tok cat="IN">of</tok> <tok cat="JJ">kappaB-binding</tok> <tok cat="NNS">proteins</tok><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <tok cat="DT">this</tok> <tok cat="NN">translocation</tok> <tok cat="VBZ">is</tok> <tok cat="VBN">enhanced</tok> <tok cat="IN">by</tok> <tok cat="DT">the</tok> <tok cat="NN">combination</tok> <tok cat="IN">of</tok> <tok cat="JJ">anti-CD3</tok> <tok cat="CC">and</tok> <tok cat="NN">FGF-1</tok><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1022982009@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="DT">This</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">binding</tok> <tok cat="NN">complex</tok> <tok cat="VBZ">is</tok> <tok cat="VBN">composed</tok> <tok cat="IN">of</tok> <tok cat="RB">transcriptionally</tok> <tok cat="JJ">active</tok> <tok cat="NN">p65</tok><tok cat="LRB">(</tok><tok cat="NN">RelA</tok><tok cat="RRB">)</tok><tok cat="NN">/p50</tok> <tok cat="NNS">heterodimers</tok> <tok cat="CC">and</tok> <tok cat="VBZ">results</tok> <tok cat="RB">primarily</tok> <tok cat="IN">from</tok> <tok cat="DT">the</tok> <tok cat="VBN">targeted</tok> <tok cat="NN">degradation</tok> <tok cat="IN">of</tok> <tok cat="NN">IkappaB-alpha</tok><tok cat="COMMA">,</tok> <tok cat="DT">an</tok> <tok cat="NN">inhibitor</tok> <tok cat="WDT">that</tok> <tok cat="VBZ">sequesters</tok> <tok cat="NN">Rel/kappaB</tok> <tok cat="IN">in</tok> <tok cat="DT">the</tok> <tok cat="NN">cytoplasm</tok><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1022982010@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="DT">These</tok> <tok cat="NNS">data</tok> <tok cat="VBP">are</tok> <tok cat="DT">the</tok> <tok cat="JJ">first</tok> <tok cat="TO">to</tok> <tok cat="VB">show</tok> <tok cat="DT">a</tok> <tok cat="NN">connection</tok> <tok cat="IN">between</tok> <tok cat="NN">FGF-1</tok> <tok cat="NN">signaling</tok> <tok cat="CC">and</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok> <tok cat="IN">outside</tok> <tok cat="IN">of</tok> <tok cat="JJ">embryonic</tok> <tok cat="NN">development</tok><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1022982011@GENIA Treebank@formal@@1@S@<cons cat="S"><tok cat="DT">The</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">events</tok> <tok cat="WDT">that</tok> <tok cat="VBP">link</tok> <tok cat="NN">FGF</tok> <tok cat="NN">receptor-1</tok> <tok cat="NN">engagement</tok> <tok cat="CC">and</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok> <tok cat="IN">in</tok> <tok cat="NN">Jurkat</tok> <tok cat="VBP">are</tok> <tok cat="RB">probably</tok> <tok cat="JJ">distinct</tok> <tok cat="IN">from</tok> <tok cat="DT">the</tok> <tok cat="NN">CD28</tok> <tok cat="NN">costimulation</tok> <tok cat="NN">pathway</tok><tok cat="COMMA">,</tok> <tok cat="IN">since</tok> <tok cat="JJ">FGF-1-induced</tok> <tok cat="NN">Rel/kappaB</tok> <tok cat="NN">binding</tok> <tok cat="NNS">proteins</tok> <tok cat="VBP">do</tok> <tok cat="RB">not</tok> <tok cat="VB">contain</tok> <tok cat="JJ">significant</tok> <tok cat="NNS">levels</tok> <tok cat="IN">of</tok> <tok cat="NN">c-Rel</tok> <tok cat="CC">and</tok> <tok cat="VBP">are</tok> <tok cat="RB">not</tok> <tok cat="JJ">identical</tok> <tok cat="IN">with</tok> <tok cat="DT">the</tok> <tok cat="NN">CD28</tok> <tok cat="NN">response</tok> <tok cat="NN">complex</tok><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1022983701@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">USF/c-Myc</tok></cons> <cons cat="VP"><tok cat="VBZ">enhances</tok><cons cat="NP" ref="i1" null="RNR"></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Yin-Yang</tok> <tok cat="CD">1</tok></cons> <cons cat="VP"><tok cat="VBZ">suppresses</tok><cons cat="NP" ref="i1" null="RNR"></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i1"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CXCR4</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">coreceptor</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">entry</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1022983702@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">USF1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">USF2</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">up-regulate</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="PP"><tok cat="FW">i.e.</tok><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="JJ">long</tok> <tok cat="JJ">terminal</tok> <tok cat="NNS">repeats</tok></cons></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">E</tok> <tok cat="NN">box</tok></cons> <cons cat="SBAR" ref="i2" null="ICH"></cons></cons></cons><cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">target</tok> <tok cat="NNS">promoters</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR" id="i2"><cons cat="WHNP" id="i3"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="VBG">binding</tok> <tok cat="NN">site</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">c-Myc</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1022983703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">c-Myc</tok> <tok cat="NN">oncoprotein</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">important</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">cellular</tok> <tok cat="NN">proliferation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="NN">Yin-Yang</tok> <tok cat="CD">1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">YY1</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">control</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">number</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">cellular</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><cons cat="NP" id="i5"><tok cat="NNS">genes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1022983704@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="CD">two</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><cons cat="ADVP"><tok cat="RB">physically</tok></cons> <tok cat="VBP">interact</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">each</tok> <tok cat="JJ">other</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">mutually</tok></cons> <tok cat="VBP">inhibit</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="JJ">respective</tok> <tok cat="JJ">biological</tok> <tok cat="NNS">functions</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1022983705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">USF/c-Myc</tok></cons> <cons cat="VP"><tok cat="VBZ">up-regulates</tok><cons cat="NP" ref="i6" null="RNR"></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">YY1</tok></cons> <cons cat="VP"><tok cat="VBZ">down-regulates</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons></cons></cons><cons cat="NP" id="i6"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CXCR4</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">coreceptor</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="JJ">cell-tropic</tok> <tok cat="NN">HIV-1</tok> <tok cat="NN">entry</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1022983706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">identified</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">E</tok> <tok cat="NN">box</tok></cons> <cons cat="PP"><tok cat="IN">around</tok> <cons cat="NP"><tok cat="CD">-260</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">YY1</tok> <tok cat="NN">binding</tok> <tok cat="NN">site</tok></cons> <cons cat="PP"><tok cat="IN">around</tok> <cons cat="NP"><tok cat="CD">-300</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="JJ">relative</tok> <tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transcription</tok> <tok cat="NN">start</tok> <tok cat="NN">site</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1022983707@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Mutation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">E</tok> <tok cat="NN">box</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">abolished</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">USF/c-Myc- mediated</tok> <tok cat="NN">up-regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CXCR4</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">mutation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">YY1</tok> <tok cat="NN">binding</tok> <tok cat="NN">site</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="VBN">associated</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">unresponsiveness</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">YY1-mediated</tok> <tok cat="NN">inhibition</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1022983708@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i7" role="SBJ"><cons cat="NP"><tok cat="NN">USF/c-Myc</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">YY1</tok></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">play</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">important</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">HIV-1-replicative</tok> <tok cat="NN">cycle</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">modulating</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NN">fusion/entry</tok> <tok cat="NN">process</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1022984101@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="VBG">Signaling</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">lymphotoxin-beta</tok> <tok cat="NN">receptor</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">stimulates</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">replication</tok></cons> <cons cat="UCP" syn="COOD"><cons cat="ADVP"><tok cat="RB">alone</tok></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cooperation</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">soluble</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">membrane-bound</tok> <tok cat="NN">TNF-alpha</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1022984102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">level</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">ongoing</tok> <tok cat="NN">HIV-1</tok> <tok cat="NN">replication</tok></cons></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">individual</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">critical</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">pathogenesis</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1022984103@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Among</tok> <cons cat="NP"><tok cat="NN">host</tok> <tok cat="JJ">immune</tok> <tok cat="NNS">factors</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i1" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">cytokine</tok> <tok cat="NN">TNF-alpha</tok></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="ADVP"><tok cat="RB">previously</tok></cons> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">increase</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">replication</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="JJ">various</tok> <cons cat="NP"><tok cat="NN">monocyte</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">model</tok> <tok cat="NNS">systems</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1022984104@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="VBG">signaling</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">TNF</tok> <tok cat="NN">receptor</tok> <tok cat="NN">family</tok> <tok cat="NN">member</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">lymphotoxin-beta</tok> <tok cat="LRB">(</tok><tok cat="NN">LT-beta</tok><tok cat="RRB">)</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">LT-betaR</tok></cons><tok cat="RRB">)</tok></cons></cons></cons><tok cat="COMMA">,</tok></cons></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBZ">regulates</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">replication</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1022984105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><tok cat="NN">HIV-1</tok> <tok cat="NN">replication</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">cooperatively</tok></cons> <cons cat="VP"><tok cat="VBN">stimulated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="SBAR" adv="TMP"><tok cat="WRB">when</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i3" role="SBJ"><tok cat="DT">the</tok> <tok cat="JJ">distinct</tok> <cons cat="NP"><tok cat="NN">LT-betaR</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">TNF</tok> <tok cat="NN">receptor</tok> <tok cat="NNS">systems</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">simultaneously</tok></cons> <cons cat="VP"><tok cat="VBN">engaged</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="PRPP">their</tok> <tok cat="JJ">specific</tok> <tok cat="NNS">ligands</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1022984106@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">physiological</tok> <tok cat="NN">coculture</tok> <tok cat="JJ">cellular</tok> <tok cat="NN">assay</tok> <tok cat="NN">system</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="JJ">membrane-bound</tok> <tok cat="NN">TNF-alpha</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">LT-alpha1beta2</tok></cons></cons> <cons cat="VP"><tok cat="VBP">act</tok> <cons cat="ADVP"><tok cat="RB">virtually</tok></cons> <cons cat="PP"><cons cat="ADVP"><tok cat="RB">identically</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="JJ">soluble</tok> <tok cat="NNS">forms</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">replication</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1022984107@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Thus</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">cosignaling</tok></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">LT-beta</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons></cons> <tok cat="NNS">receptors</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">probably</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">modulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">replication</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">subsequent</tok> <tok cat="NN">determination</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="JJ">viral</tok> <tok cat="NN">burden</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1022984108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Intriguingly</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="NN">surface</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">LT-alpha1beta2</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="RB">up-</tok><tok cat="VBN">regulated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok></cons> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">acutely</tok></cons> <tok cat="VBN">infected</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">suggesting</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">positive</tok> <tok cat="NN">feedback</tok> <tok cat="NN">loop</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">infection</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">LT-alpha1beta2</tok> <tok cat="NN">expression</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">replication</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1022984109@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Given</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">critical</tok> <tok cat="NN">role</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">LT-alpha1beta2</tok></cons> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP" ref="i5" null="T"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">lymphoid</tok> <tok cat="NN">architecture</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">speculate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="NN">LT-alpha1beta2</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">HIV-associated</tok> <tok cat="NNS">abnormalities</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">organs</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1023134501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="NN">Glucocorticoid</tok> <tok cat="NNS">receptors</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">down-regulated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">inflamed</tok> <tok cat="JJ">colonic</tok> <tok cat="NN">mucosa</tok></cons></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">inflammatory</tok> <tok cat="NN">bowel</tok> <tok cat="NN">disease</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">[</tok><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VB">see</tok> <cons cat="NP"><tok cat="NNS">comments</tok></cons></cons></cons><tok cat="RRB">]</tok></cons></cons></cons></cons>@@@@1@25@@oe@16-12-2010 1023134502@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">BACKGROUND</tok><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="VBG">Growing</tok> <tok cat="NN">evidence</tok></cons> <cons cat="VP"><tok cat="VBZ">indicates</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">immune</tok> <tok cat="NN">system</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">hypothalamic-pituitary-adrenal</tok> <tok cat="NN">system</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">linked</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="JJ">several</tok> <tok cat="NNS">mechanisms</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">example</tok></cons></cons> <cons cat="NP"><tok cat="JJ">intracellular</tok> <tok cat="NN">glucocorticoid</tok> <tok cat="NNS">receptors</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">hGR</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1023134503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NNS">Glucocorticoids</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">standard</tok> <tok cat="NN">treatment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">acute</tok> <tok cat="NNS">attacks</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">inflammatory</tok> <tok cat="NN">bowel</tok> <tok cat="NN">disease</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IBD</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1023134504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">glucocorticoids</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">hGR</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">down-regulates</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">inflammatory</tok> <tok cat="NNS">genes</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">propagate</tok> <cons cat="NP"><tok cat="NN">IBD</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1023134505@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">PATIENTS</tok></cons> <tok cat="CC">AND</tok> <cons cat="NP"><tok cat="NNS">METHODS</tok></cons><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="NN">IBD</tok> <tok cat="NNS">patients</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">either</tok></cons> <cons cat="VP"><tok cat="VBN">treated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">5-60</tok> <tok cat="NN">mg</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">prednisolone</tok></cons></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="QP"><tok cat="JJR">more</tok> <tok cat="IN">than</tok> <tok cat="CD">1</tok></cons> <tok cat="NN">week</tok></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="PP" role="PRD"><tok cat="IN">without</tok> <cons cat="NP"><tok cat="NN">glucocorticoid</tok> <tok cat="NN">treatment</tok></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="QP"><tok cat="JJR">more</tok> <tok cat="IN">than</tok> <tok cat="CD">4</tok></cons> <tok cat="NNS">weeks</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1023134506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NN">hGR</tok> <tok cat="NNS">levels</tok></cons> <tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">determined</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="VBN">isolated</tok> <tok cat="NN">cytosol</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">PBMCs</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">mucosal</tok> <tok cat="NNS">biopsies</tok></cons> <cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">radioassay</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">[3H]-dexamethasone</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1023134507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Interleukin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CD">6</tok> <tok cat="NNS">levels</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">determined</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="JJ">enzyme-linked</tok> <tok cat="JJ">immunosorbent</tok> <tok cat="NN">assay</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">ELISA</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1023134508@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NNS">RESULTS</tok><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">systemic</tok> <tok cat="LRB">(</tok><tok cat="NN">PBMC</tok><tok cat="RRB">)</tok> <tok cat="NN">hGR</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">corticosteroid-treated</tok> <tok cat="NN">IBD</tok> <tok cat="NNS">patients</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="ADJP" role="PRD"><cons cat="ADJP"><tok cat="JJR">lower</tok></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="CD">59.6</tok> <tok cat="CC">+/-</tok> <tok cat="CD">57.1</tok> <tok cat="NN">dpm</tok> <tok cat="NN">mg-1</tok> <tok cat="NN">cytosol</tok> <tok cat="NN">protein</tok></cons> <tok cat="CC">vs.</tok> <cons cat="NP"><tok cat="CD">227.0</tok> <tok cat="CC">+/-</tok> <tok cat="CD">90.8</tok> <tok cat="NN">dpm</tok> <tok cat="NN">mg-1</tok> <tok cat="NN">cytosol</tok> <tok cat="NN">protein</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">P</tok></cons> <cons cat="VP"><tok cat="JJ">=</tok> <cons cat="NP" role="PRD"><tok cat="CD">0.007</tok></cons></cons></cons></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">IBD</tok> <tok cat="NNS">patients</tok></cons> <cons cat="VP"><tok cat="RB">not</tok> <tok cat="VBG">receiving</tok> <cons cat="NP"><tok cat="NN">glucocorticoid</tok> <tok cat="NN">treatment</tok></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="CD">179.7</tok> <tok cat="CC">+/-</tok> <tok cat="CD">171.3</tok> <tok cat="NN">dpm</tok> <tok cat="NN">mg-1</tok> <tok cat="NN">cytosol</tok> <tok cat="NN">protein</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">P</tok></cons> <cons cat="VP"><tok cat="JJ">=</tok> <cons cat="NP" role="PRD"><tok cat="CD">0.002</tok></cons></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@63@@oe@16-12-2010 1023134509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Systemic</tok> <tok cat="NN">hGR</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">untreated</tok> <tok cat="NN">IBD</tok> <tok cat="NNS">patients</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">differ</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1023134510@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">connective</tok> <tok cat="NN">tissue</tok> <tok cat="NNS">diseases</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7" role="SBJ"><tok cat="JJ">systemic</tok> <tok cat="NN">hGR</tok> <tok cat="NNS">levels</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="S"><cons cat="NP" ref="i7" id="i8" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">decreased</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">glucocorticoid</tok> <tok cat="NN">treatment</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1023134511@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Systemic</tok> <tok cat="NN">hGR</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Crohn</tok><tok cat="POS">'s</tok> <tok cat="NN">disease</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">CD</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">treated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NNS">steroids</tok></cons></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">66.6</tok> <tok cat="CC">+/-</tok> <tok cat="CD">61.0</tok> <tok cat="NN">dpm</tok> <tok cat="NN">mg-1</tok> <tok cat="NN">cytosol</tok> <tok cat="NN">protein</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <tok cat="RB">not</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">different</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">ulcerative</tok> <tok cat="NN">colitis</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">UC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">56.1</tok> <tok cat="CC">+/-</tok> <tok cat="CD">51.6</tok> <tok cat="NN">dpm</tok> <tok cat="NN">mg-1</tok> <tok cat="NN">cytosol</tok> <tok cat="NN">protein</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@47@@oe@16-12-2010 1023134512@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">contrast</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">findings</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i9" role="SBJ"><tok cat="JJ">mucosal</tok> <tok cat="NN">hGR</tok> <tok cat="NNS">levels</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBN">decreased</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="DT">both</tok> <cons cat="NP"><tok cat="JJ">steroid-treated</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">18.0</tok> <tok cat="CC">+/-</tok> <tok cat="CD">15.5</tok></cons><tok cat="RRB">)</tok></cons> <cons cat="NP" ref="i10" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="RB">not</tok> <tok cat="JJ">steroid-treated</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">37.8</tok> <tok cat="CC">+/-</tok> <tok cat="CD">30.5</tok></cons><tok cat="RRB">)</tok></cons> <cons cat="NP" ref="i10" null="RNR"></cons></cons><cons cat="NP" id="i10"><tok cat="NNS">patients</tok></cons></cons></cons> <cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">125.6</tok> <tok cat="CC">+/-</tok> <tok cat="CD">97.1</tok></cons><tok cat="COLON">;</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">P</tok></cons> <cons cat="VP"><tok cat="JJ">=</tok> <cons cat="NP" role="PRD"><tok cat="CD">0.00009</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">P</tok></cons> <cons cat="VP"><tok cat="JJ">=</tok> <cons cat="NP" role="PRD"><tok cat="CD">0.0008</tok></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">respectively</tok></cons></cons></cons> <tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@48@@oe@16-12-2010 1023134513@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">IL-6</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">all</tok> <tok cat="NN">IBD</tok> <tok cat="NNS">groups</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" ref="i11" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="NP" ref="i11" null="RNR"></cons></cons><cons cat="NP" id="i11"><tok cat="NNS">steroids</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">different</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1023134514@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">CONCLUSION</tok><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">IBD</tok></cons></cons> <cons cat="NP" role="SBJ"><tok cat="EX">there</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP"><tok cat="DT">no</tok> <tok cat="NN">difference</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">systemic</tok> <tok cat="NN">hGR</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="RB">not</tok> <tok cat="JJ">steroid-treated</tok> <tok cat="NNS">patients</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">spite</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">inflammatory</tok> <tok cat="NN">activity</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-6</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1023134515@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i12" role="SBJ"><tok cat="JJ">Mucosal</tok> <tok cat="NN">hGR</tok> <tok cat="NNS">levels</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">decreased</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">independently</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">treatment</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">probably</tok></cons> <cons cat="VP"><tok cat="VBG">leading</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="VBN">decreased</tok> <tok cat="NN">protection</tok></cons> <cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">action</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">intestinal</tok> <tok cat="NN">mucosa</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1023238501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Resistance</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok> <tok cat="JJ">induced</tok> <tok cat="NN">apoptosis</tok></cons> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">correlates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">high</tok> <tok cat="JJ">metastatic</tok> <tok cat="NN">capacity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">cells</tok></cons> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vivo</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1023238502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">TNF</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="CD">one</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">cytokines</tok></cons> <cons cat="VP"><tok cat="VBN">secreted</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">immune</tok> <tok cat="NN">system</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1023238503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">those</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons> <cons cat="VP"><tok cat="VBG">lacking</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">capability</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">form</tok> <cons cat="NP"><tok cat="JJ">metastatic</tok> <tok cat="NNS">tumors</tok></cons> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vivo</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">susceptible</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="NN">TNF</tok> <tok cat="JJ">induced</tok></cons> <tok cat="NN">apoptosis</tok></cons></cons> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1023238504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">high</tok> <tok cat="JJ">metastatic</tok> <tok cat="NN">potential</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">resistant</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">TNF</tok></cons> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1023238505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="JJ">same</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">resistant</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cytolytic</tok> <tok cat="NN">action</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="JJ">cytotoxic</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="VP"><tok cat="VBN">secreted</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">LAK</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1023238506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">TNF</tok> <tok cat="NN">resistance</tok></cons> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">correlates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">increased</tok> <tok cat="NN">level</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1023238507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">finding</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">provide</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">tool</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1" null="ZERO"></cons><cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">improve</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">current</tok> <tok cat="NNS">protocols</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">immunotherapy</tok></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">insights</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="SBAR"><cons cat="WHADVP" id="i2"><tok cat="WRB">how</tok></cons> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="NN">tumor</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP" ref="i3" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="VP"><tok cat="VBP">are</tok> <tok cat="RB">not</tok> <cons cat="VP" ref="i3" null="RNR"></cons></cons><cons cat="VP" id="i3"><tok cat="VBN">killed</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">LAK</tok> <tok cat="NNS">cells</tok></cons></cons></cons><cons cat="ADVP" ref="i2" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1023387501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">C5a-induced</tok> <tok cat="NN">interleukin-8</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1023387502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">C5a</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">potent</tok> <tok cat="NN">peptide</tok> <tok cat="NN">chemoattractant</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">stimulates</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin-8</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-8</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">secretion</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">PBMC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1023387503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NNS">Experiments</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">conducted</tok> <tok cat="TO">to</tok> <tok cat="VB">understand</tok> <tok cat="DT">the</tok> <tok cat="NNS">mechanisms</tok> <tok cat="IN">for</tok> <tok cat="JJ">C5a-induced</tok> <tok cat="NN">IL-8</tok> <tok cat="NN">production</tok><tok cat="COMMA">,</tok> <tok cat="WDT">which</tok> <tok cat="VBD">was</tok> <tok cat="JJ">14-fold</tok> <tok cat="JJR">greater</tok> <tok cat="IN">than</tok> <tok cat="DT">that</tok> <tok cat="IN">in</tok> <tok cat="JJ">unstimulated</tok> <tok cat="NNS">cells</tok> <tok cat="IN">by</tok> <tok cat="CD">2</tok> <tok cat="NNS">hours</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1023387504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NN">IL-8</tok> <tok cat="NN">secretion</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">accompanied</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">accumulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-8</tok> <tok cat="NN">mRNA</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cytosol</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">kappaB</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="CD">30</tok> <tok cat="NNS">minutes</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1023387505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S"><cons cat="NP" syn="COOD" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">AP-1</tok></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="NN">NF-IL-6</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">C5a-stimulated</tok> <tok cat="NNS">PBMC</tok></cons></cons></cons></cons><tok cat="COLON">;</tok></cons> <cons cat="S"><cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRPP">its</tok> <tok cat="VBN">delayed</tok> <tok cat="NN">expression</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="PP" adv="TMP"><cons cat="ADJP"><tok cat="JJ">maximal</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="CD">4</tok> <tok cat="NNS">hours</tok></cons></cons></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBD">suggested</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="RBR">less</tok> <tok cat="JJ">important</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">rapid</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-8</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1023387506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">correlation</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">C5a-induced</tok> <tok cat="NN">kappaB</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-8</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">examined</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">RAW264.7</tok> <tok cat="NN">macrophage</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">reporter</tok> <tok cat="NNS">genes</tok></cons> <cons cat="VP"><tok cat="VBN">directed</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">kappaB</tok> <tok cat="NN">sequence</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IkappaBalpha</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-8</tok> <tok cat="NN">promoter</tok> <tok cat="NNS">regions</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1023387507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="JJ">C5a-induced</tok> <tok cat="NN">reporter</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">abolished</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">introducing</tok> <cons cat="NP"><tok cat="NNS">mutations</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">kappaB</tok> <tok cat="NNS">sites</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">coexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dominant</tok> <tok cat="JJ">negative</tok> <tok cat="NN">IkappaBalpha</tok> <tok cat="NN">construct</tok></cons> <cons cat="ADJP"><tok cat="JJ">resistant</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">agonist-induced</tok> <tok cat="NN">phosphorylation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1023387508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Pertussis</tok> <tok cat="NN">toxin</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">ADP-ribosylates</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Gi</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">couple</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">C5a</tok> <tok cat="NN">receptor</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">produced</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">minimal</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">C5a-induced</tok> <tok cat="NN">IL-8</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><tok cat="JJ">little</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">C5a-induced</tok> <tok cat="NN">calcium</tok> <tok cat="NN">mobilization</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">RAW264.7</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1023387509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">C5a-induced</tok> <tok cat="NN">IL-8</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="DT">this</tok> <tok cat="NN">response</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">primarily</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">pertussis</tok> <tok cat="JJ">toxin-insensitive</tok> <tok cat="NN">pathway</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1023387901@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Transcriptional</tok> <tok cat="NN">targeting</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">retroviral</tok> <tok cat="NNS">vectors</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">erythroblastic</tok> <tok cat="NN">progeny</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">transduced</tok> <tok cat="JJ">hematopoietic</tok> <tok cat="NN">stem</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1023387902@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="VBN">Targeted</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">specific</tok> <tok cat="NNS">tissues</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NNS">lineages</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">necessary</tok> <tok cat="NN">feature</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">gene</tok> <tok cat="NN">therapy</tok> <tok cat="NN">vector</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">many</tok> <tok cat="JJ">clinical</tok> <tok cat="NNS">applications</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">correction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">hemoglobinopathies</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NNS">thalassemias</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">transplantation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="RB">genetically</tok> <tok cat="VBN">modified</tok> <tok cat="JJ">hematopoietic</tok> <tok cat="NN">stem</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1023387903@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">developed</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">retroviral</tok> <tok cat="NNS">vectors</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i1"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">constitutive</tok> <tok cat="JJ">viral</tok> <tok cat="NN">enhancer</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">U3</tok> <tok cat="NN">region</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">3'</tok> <tok cat="NN">LTR</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">replaced</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">autoregulatory</tok> <tok cat="NN">enhancer</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">erythroid-specific</tok> <tok cat="NN">GATA-1</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons><cons cat="PP" ref="i1" null="T"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1023387904@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="DT">The</tok> <tok cat="VBN">replaced</tok> <tok cat="NN">enhancer</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">propagated</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">5'</tok> <tok cat="NN">LTR</tok></cons></cons> <cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">integration</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">target</tok> <tok cat="NN">cell</tok> <tok cat="NN">genome</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1023387905@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="DT">The</tok> <tok cat="VBN">modified</tok> <tok cat="NNS">vectors</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">transduce</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">hematopoietic</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">cord</tok> <tok cat="JJ">blood-derived</tok> <tok cat="JJ">CD34(+)</tok> <tok cat="NN">stem/progenitor</tok> <tok cat="NNS">cells</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">murine</tok> <tok cat="NN">bone</tok> <tok cat="NN">marrow</tok> <tok cat="VBG">repopulating</tok> <tok cat="NN">stem</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1023387906@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">appropriate</tok> <tok cat="NN">reporter</tok> <tok cat="NNS">genes</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="NN">triangle</tok> <tok cat="NN">upLNGFR</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">EGFP</tok></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">analyzed</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="UCP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">differentiated</tok> <tok cat="NN">progeny</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">transduced</tok> <tok cat="NN">stem</tok> <tok cat="NNS">cells</tok></cons> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">liquid</tok> <tok cat="NN">culture</tok></cons></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">clonogenic</tok> <tok cat="NN">assay</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vivo</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">bone</tok> <tok cat="NN">marrow</tok> <tok cat="NN">transplantation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="RB">lethally</tok> <tok cat="JJ">irradiated</tok> <tok cat="NNS">mice</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@48@@oe@16-12-2010 1023387907@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">GATA-1</tok> <tok cat="JJ">autoregulatory</tok> <tok cat="NN">enhancer</tok></cons> <cons cat="ADVP"><tok cat="RB">effectively</tok></cons> <cons cat="VP"><tok cat="VBZ">restricts</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">LTR-driven</tok> <tok cat="JJ">proviral</tok> <tok cat="NN">transcription</tok> <tok cat="NN">unit</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">erythroblastic</tok> <tok cat="NN">progeny</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">progenitors</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">mouse-repopulating</tok> <tok cat="NN">stem</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1023387908@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" id="i6" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Packaging</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NNS">particles</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">integration</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">target</tok> <tok cat="NN">genome</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">stability</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">integrated</tok> <tok cat="NN">provirus</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">affected</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">the</tok> <tok cat="NN">LTR</tok> <tok cat="NN">modification</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1023387909@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Enhancer</tok> <tok cat="NN">replacement</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">therefore</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">effective</tok> <tok cat="NN">strategy</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="VB">target</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">retroviral</tok> <tok cat="NN">transgene</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">specific</tok> <tok cat="NN">progeny</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">transduced</tok> <tok cat="JJ">hematopoietic</tok> <tok cat="NN">stem</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1023388201@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="DT">An</tok> <tok cat="JJ">essential</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">CD34(+)</tok> <tok cat="NN">bone</tok> <tok cat="NN">marrow</tok> <tok cat="NN">cell</tok> <tok cat="NN">survival</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1023388202@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">important</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NN">activation</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">B-cell</tok> <tok cat="NN">maturation</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">immunodeficiency</tok> <tok cat="NN">virus</tok> <tok cat="NN">transcription</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">alternatively</tok></cons> <cons cat="VP"><tok cat="VBG">mediating</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">protecting</tok> <cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">variety</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NNS">types</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1023388203@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">CD34(+)</tok> <tok cat="NN">bone</tok> <tok cat="NN">marrow</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">described</tok><cons cat="NP" ref="i1" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1023388204@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">provide</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">evidence</tok></cons> <cons cat="SBAR" ref="i2" null="ICH"></cons></cons><cons cat="ADVP"><tok cat="RB">here</tok></cons> <cons cat="SBAR" id="i2"><tok cat="IN">that</tok> <cons cat="S"><cons cat="ADVP"><tok cat="RB">virtually</tok></cons> <cons cat="NP" role="SBJ"><tok cat="DT">all</tok> <tok cat="JJ">human</tok> <tok cat="JJ">CD34(+)</tok> <tok cat="NN">bone</tok> <tok cat="NN">marrow</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">express</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" id="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">exposure</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">phorbol</tok> <tok cat="NN">12-myristate</tok> <tok cat="NN">13-acetate</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">variety</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">cytokines</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="FW">eg</tok><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok> <tok cat="NN">alpha</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">interleukin-3</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">granulocyte-macrophage</tok> <tok cat="JJ">colony-stimulating</tok> <tok cat="NN">factor</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1023388205@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">CD34(+)</tok> <tok cat="NN">bone</tok> <tok cat="NN">marrow</tok> <tok cat="NN">cell</tok> <tok cat="JJ">clonogenic</tok> <tok cat="NN">function</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">survival</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1023388206@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">offer</tok> <cons cat="NP"><tok cat="NN">insight</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">new</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">maintaining</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">survival</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">function</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">hematopoietic</tok> <tok cat="NN">stem</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">progenitor</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><cons cat="NP" id="i6"><tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><tok cat="JJ">proposed</tok> <tok cat="NNS">strategies</tok></cons> <cons cat="VP"><tok cat="VBG">involving</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">adjunct</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">cancer</tok> <tok cat="NN">chemotherapy</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">should</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">approached</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">caution</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1023388801@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Unicellular-unilineage</tok> <tok cat="JJ">erythropoietic</tok> <tok cat="NNS">cultures</tok><tok cat="COLON">:</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="JJ">molecular</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">regulatory</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="NN">sibling</tok> <tok cat="NN">cell</tok> <tok cat="NN">level</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1023388802@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><cons cat="ADJP"><tok cat="FW">In</tok> <tok cat="FW">vitro</tok></cons> <tok cat="NNS">studies</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">hematopoietic</tok> <tok cat="NN">control</tok> <tok cat="NNS">mechanisms</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">hampered</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">heterogeneity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">analyzed</tok> <tok cat="NN">cell</tok> <tok cat="NNS">populations</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="FW">ie</tok><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">lack</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">lineage</tok> <tok cat="NN">specificity</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">developmental</tok> <tok cat="NN">stage</tok> <tok cat="NN">homogeneity</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">progenitor/precursor</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBG">growing</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">culture</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1023388803@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">developed</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">unicellular</tok> <tok cat="NN">culture</tok> <tok cat="NNS">systems</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">unilineage</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">purified</tok> <tok cat="JJ">hematopoietic</tok> <tok cat="NN">progenitor</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">followed</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">daughter</tok> <tok cat="NN">cell</tok> <tok cat="NN">analysis</tok></cons></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">cellular</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">molecular</tok></cons></cons> <tok cat="NN">level</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1023388804@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">culture</tok> <tok cat="NN">system</tok></cons> <cons cat="VP"><tok cat="VBN">reported</tok> <cons cat="NP" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">here</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">1</tok><tok cat="RRB">)</tok></cons> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">growth</tok> <tok cat="NN">factor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">GF</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">stimulus</tok></cons> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">cord</tok> <tok cat="NN">blood</tok> <tok cat="LRB">(</tok><tok cat="NN">CB</tok><tok cat="RRB">)</tok> <tok cat="NN">progenitor</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">proliferate</tok></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VB">differentiate/mature</tok></cons> <cons cat="ADVP"><tok cat="RB">exclusively</tok></cons> <cons cat="PP"><tok cat="IN">along</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">erythroid</tok> <tok cat="NN">lineage</tok></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok></cons> <cons cat="S"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">2</tok><tok cat="RRB">)</tok></cons> <cons cat="NP" id="i2" role="SBJ"><tok cat="DT">this</tok> <tok cat="JJ">erythropoietic</tok> <tok cat="NN">wave</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">characterized</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="QP"><tok cat="JJR">less</tok> <tok cat="IN">than</tok> <tok cat="CD">4</tok></cons><tok cat="NN">%</tok> <tok cat="JJ">apoptotic</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="COLON">;</tok></cons> <cons cat="S" syn="COOD"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">3</tok><tok cat="RRB">)</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">asymmetric</tok> <tok cat="NNS">divisions</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">virtually</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">absent</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="FW">ie</tok><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="JJ">nonresponsive</tok> <tok cat="JJ">hematopoietic</tok> <tok cat="NNS">progenitors</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">no</tok> <tok cat="JJ">erythropoietic</tok> <tok cat="NN">potential</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">forced</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons></cons></cons><tok cat="COLON">;</tok></cons> <cons cat="S" syn="COOD"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">4</tok><tok cat="RRB">)</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">system</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><cons cat="ADJP"><tok cat="NN">cell</tok> <tok cat="NN">division</tok> <tok cat="JJ">controlled</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">cdc</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="FW">ie</tok><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">number</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">divisions</tok></cons> <cons cat="VP"><tok cat="VBN">performed</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">each</tok> <tok cat="NN">cell</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">monitored</tok><cons cat="NP" ref="i4" null="NONE"></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@100@@oe@16-12-2010 1023388805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Single-cell</tok> <tok cat="NN">reverse</tok> <tok cat="NN">transcriptase-polymerase</tok> <tok cat="NN">chain</tok> <tok cat="NN">reaction</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">RT-PCR</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">analysis</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">applied</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">culture</tok> <tok cat="NN">system</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">investigate</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">diverse</tok> <tok cat="NNS">receptors</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NNS">markers</tok> <tok cat="IN">of</tok> <tok cat="NN">differentiation</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">EKLF</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">GATA-2</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">p45</tok> <tok cat="NN">NF-E2</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">PU.1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">SCL/Tal1</tok></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">discrete</tok> <tok cat="NNS">stages</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">erythropoietic</tok> <tok cat="NN">development</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@52@@oe@16-12-2010 1023388806@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="ADJP"><tok cat="RB">Freshly</tok> <tok cat="VBN">isolated</tok></cons> <tok cat="JJ">CD34(+)</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">expressed</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CD34</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">c-kit</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">PU.1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">GATA-2</tok></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">express</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CD36</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">erythropoietin</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">EpoR</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">SCL/Tal1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">EKLF</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">NF-E2</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">glyocophorin</tok> <tok cat="NN">A</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">GPA</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1023388807@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="JJ">early</tok></cons></cons> <cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="JJ">intermediate</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">stages</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">monitored</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CD36</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">Tal1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">EKLF</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">NF-E2</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">preceeded</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">EpoR</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1023388808@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">late</tok> <tok cat="NNS">stages</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">maturation</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7" role="SBJ"><tok cat="NN">GPA</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">upregulated</tok><cons cat="NP" ref="i7" null="NONE"></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="NP" syn="COOD" id="i8" role="SBJ"><cons cat="NP"><tok cat="NN">CD34</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">c-kit</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">PU.1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">GATA-2</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP" syn="COOD"><cons cat="ADVP"><tok cat="RB">barely</tok></cons> <tok cat="CC">or</tok> <cons cat="ADVP"><tok cat="RB">not</tok></cons></cons> <cons cat="VP"><tok cat="VBN">detected</tok><cons cat="NP" ref="i8" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1023388809@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i9" role="SBJ"><tok cat="JJ">competitive</tok> <tok cat="JJ">single-cell</tok> <tok cat="NN">RT-PCR</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">assay</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD34</tok> <tok cat="NN">mRNA</tok> <tok cat="NNS">transcripts</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">sibling</tok> <tok cat="JJ">CD34(+)</tok> <tok cat="JJ">CD38(-)</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBG">differentiating</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">unilineage</tok> <tok cat="JJ">erythroid</tok> <tok cat="NNS">cultures</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">this</tok> <tok cat="NN">analysis</tok></cons> <cons cat="VP"><tok cat="VBD">allowed</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">us</tok></cons> <cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">semiquantitate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">gradual</tok> <tok cat="NN">downmodulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CD34</tok> <tok cat="NN">mRNA</tok></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">progenitor</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="VBG">differentiating</tok> <tok cat="JJ">erythroid</tok> <tok cat="NN">progeny</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@45@@oe@16-12-2010 1023388810@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">It</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">concluded</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">this</tok> <tok cat="JJ">novel</tok> <tok cat="NN">culture</tok> <tok cat="NN">system</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">coupled</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">single-cell</tok> <tok cat="NN">RT-PCR</tok> <tok cat="NN">analysis</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">eliminate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">ambiguities</tok></cons> <cons cat="ADJP"><tok cat="JJ">intrinsic</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">molecular</tok> <tok cat="NNS">studies</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">heterogeneous</tok> <tok cat="NNS">populations</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">hematopoietic</tok> <tok cat="NNS">progenitors/precursors</tok></cons> <cons cat="VP"><tok cat="VBG">growing</tok> <cons cat="PP"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">culture</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">particularly</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">initial</tok> <tok cat="NNS">stages</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">development</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1023392701@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">cycle</tok> <tok cat="NN">entry</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="VP"><tok cat="VBN">infected</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="JJ">Epstein-Barr</tok> <tok cat="NN">virus</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1023392702@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Infection</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">Epstein-Barr</tok> <tok cat="NN">virus</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">EBV</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">results</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">cycle</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">growth</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1023392703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">interpret</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i1"><tok cat="IN">by</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">EBV</tok></cons> <cons cat="VP"><tok cat="VBZ">activates</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cell</tok></cons><cons cat="PP" ref="i1" null="T"></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">assayed</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">many</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">G0</tok> <cons cat="NP" ref="i2" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">G1</tok> <cons cat="NP" ref="i2" null="RNR"></cons></cons><cons cat="NP" id="i2"><tok cat="NNS">phases</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cell</tok> <tok cat="NN">cycle</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1023392704@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">EBV</tok> <tok cat="NN">infection</tok></cons></cons> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJS">most</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">changes</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">early</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cyclin</tok> <tok cat="NN">D2</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">dependent</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">EBV</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">alteration</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">E2F-4</tok> <tok cat="NN">profile</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">partly</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">independent</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S" func="ADV"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">presumably</tok></cons> <cons cat="VP"><tok cat="VBG">occurring</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">signal</tok> <tok cat="NN">transduction</tok></cons> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" null="NONE"></cons><cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i4"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">virus</tok></cons> <cons cat="VP"><tok cat="VBZ">binds</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">receptor</tok><tok cat="COMMA">,</tok> <tok cat="NN">CD21</tok></cons></cons><cons cat="ADVP" ref="i4" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@57@@oe@16-12-2010 1023392705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">By</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">comparing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">genes</tok></cons> <cons cat="VP"><tok cat="VBG">controlling</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="VP"><tok cat="VBG">encoding</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">several</tok> <tok cat="NNS">members</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">BCL-2</tok> <tok cat="NN">family</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">proteins</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">known</tok> <tok cat="JJ">relative</tok> <tok cat="NN">resistance</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">EBV-immortalized</tok> <tok cat="NN">B-cell</tok> <tok cat="NNS">lines</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">apoptosis</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">low</tok> <tok cat="NN">serum</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">correlate</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">BCL-2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">A20</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@47@@oe@16-12-2010 1023392706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="NN">A20</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">regulated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i7"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i7" id="i8" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="S"><cons cat="NP" ref="i8" id="i9" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">the</tok> <tok cat="NN">EBV</tok> <tok cat="NN">LMP-1</tok> <tok cat="NN">protein</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1023392707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Quantitative</tok> <tok cat="NNS">assays</tok></cons> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">direct</tok> <tok cat="JJ">temporal</tok> <tok cat="NN">relationship</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">LMP-1</tok> <tok cat="NN">protein</tok> <tok cat="NNS">levels</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">active</tok> <tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">time</tok> <tok cat="NN">course</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">infection</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1023394701@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">Immortalization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">CD4(+)</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">CD8(+)</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">leukemia</tok> <tok cat="NN">virus</tok> <tok cat="NN">type</tok> <tok cat="CD">1</tok> <tok cat="NN">Tax</tok> <tok cat="NNS">mutants</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">functional</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">clone</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1023394702@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="DT">The</tok> <tok cat="JJ">human</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">leukemia</tok> <tok cat="NN">virus</tok> <tok cat="NN">type</tok> <tok cat="CD">1</tok> <tok cat="LRB">(</tok><tok cat="NN">HTLV-1</tok><tok cat="RRB">)</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">trans-activator</tok> <tok cat="NN">Tax</tok></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">demonstrated</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">have</tok> <cons cat="NP"><tok cat="VBG">transforming</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">multiple</tok> <tok cat="NN">cell</tok> <tok cat="NN">culture</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">transgenic-mouse</tok> <tok cat="NNS">models</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1023394703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBG">activating</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="JJ">long</tok> <tok cat="JJ">terminal</tok> <tok cat="NN">repeat</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">LTR</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cyclic</tok> <tok cat="NN">AMP</tok> <tok cat="NN">response</tok> <tok cat="NN">element</tok> <tok cat="NN">binding</tok> <tok cat="VBG">protein/activating</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="LRB">(</tok><tok cat="NN">CREB/ATF</tok><tok cat="RRB">)</tok> <tok cat="NN">family</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">Tax</tok></cons> <cons cat="VP"><tok cat="VBZ">activates</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">multiple</tok> <tok cat="JJ">cellular</tok> <tok cat="NNS">promoters</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">pathway</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@48@@oe@16-12-2010 1023394704@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">Tax</tok> <tok cat="NNS">mutants</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">M22</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">M47</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="ADVP"><tok cat="RB">previously</tok></cons> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">demonstrated</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="ADVP"><tok cat="RB">selectively</tok></cons> <cons cat="VP"><tok cat="VB">abrogate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ability</tok> <cons cat="S" ref="i4" null="ICH"></cons></cons><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Tax</tok></cons></cons> <cons cat="S" id="i4"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">CREB/ATF</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><cons cat="NP" id="i5"><tok cat="NN">pathway</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">respectively</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1023394705@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">mutations</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">introduced</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">tax</tok> <tok cat="NN">gene</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ACH</tok> <tok cat="JJ">functional</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">clone</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HTLV-1</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><tok cat="NN">virus</tok></cons> <cons cat="VP"><tok cat="VBN">produced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">mutant</tok> <tok cat="NN">ACH</tok> <tok cat="NNS">clones</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">examined</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ability</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">replicate</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><tok cat="VB">immortalize</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><cons cat="NP" id="i8"><tok cat="JJ">primary</tok> <tok cat="JJ">human</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1023394706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" func="ADV"><tok cat="IN">While</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">virus</tok></cons> <cons cat="VP"><tok cat="VBN">derived</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">clone</tok></cons> <cons cat="VP"><tok cat="VBG">containing</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">M47</tok> <tok cat="NN">mutation</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">retained</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ability</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">immortalize</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">M22</tok> <tok cat="NN">mutant</tok></cons> <cons cat="VP"><tok cat="VBD">lost</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ability</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">immortalize</tok> <cons cat="NP"><tok cat="JJ">infected</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1023394707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">CREB/ATF</tok> <tok cat="NN">pathway</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">Tax</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">dispensable</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">immortalization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">HTLV-1</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">pathway</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">critical</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1023547601@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">oestrogen</tok> <tok cat="NN">receptor</tok> <tok cat="NN">codon</tok> <tok cat="CD">10</tok> <tok cat="NN">polymorphism</tok></cons> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">breast</tok> <tok cat="NN">cancer</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">present</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">non-malignant</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1023547602@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">oestrogens</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">oestrogen-receptive</tok> <tok cat="NNS">organs</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">cells</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">intracellular</tok> <tok cat="NNS">receptors</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">ERalpha</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">ERbeta</tok></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1023547603@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="NN">Oestrogen</tok> <tok cat="NN">receptor</tok> <tok cat="NN">gene</tok> <tok cat="NNS">polymorphisms</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">region</tok></cons> <cons cat="VP"><tok cat="VBG">encoding</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">N-terminal</tok> <tok cat="NN">portion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">protein</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">reportedly</tok></cons> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">pathological</tok> <tok cat="NNS">conditions</tok></cons> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">breast</tok> <tok cat="NN">cancer</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">hypertension</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">spontaneous</tok> <tok cat="NN">abortion</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">coronary</tok> <tok cat="NN">heart</tok> <tok cat="NN">disease</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1023547604@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="JJ">silent</tok> <tok cat="NN">mutation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">codon</tok> <tok cat="CD">10</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">exon</tok> <tok cat="CD">1</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">ER-negative</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">ER-positive</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><cons cat="NP" id="i4"><tok cat="JJ">human</tok> <tok cat="NN">breast</tok> <tok cat="NN">cancer</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">breast</tok> <tok cat="NNS">tumors</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">blood</tok> <tok cat="NN">DNA</tok></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">breast</tok> <tok cat="NN">cancer</tok> <tok cat="NNS">patients</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">recognized</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">polymorphic</tok> <tok cat="NN">site</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1023547605@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">examined</tok><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="VBG">denaturing</tok> <tok cat="JJ">gradient-gel</tok> <tok cat="NN">electrophoresis</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NN">sequence</tok> <tok cat="NN">analysis</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">possible</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">codon</tok> <tok cat="CD">10</tok> <tok cat="JJ">polymorphic</tok> <tok cat="NN">site</tok></cons></cons></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><tok cat="JJ">normal</tok> <cons cat="NP"><tok cat="NN">oestrogen</tok> <tok cat="NN">target</tok> <tok cat="NNS">organs</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">uterus</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">myometrium</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">endometrium</tok></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">placenta</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">benign</tok> <tok cat="NN">uterus</tok> <tok cat="NN">tumour</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">leiomyoma</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@59@@oe@16-12-2010 1023547606@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP"><tok cat="NN">ER</tok> <tok cat="NN">codon</tok> <tok cat="CD">10</tok> <tok cat="NN">polymorphism</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">samples</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">compared</tok> <cons cat="NP"><tok cat="PRP">them</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">breast</tok> <tok cat="NN">cancer</tok> <tok cat="NNS">samples</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1023547607@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><tok cat="DT">All</tok> <cons cat="NP"><tok cat="NNS">tissues</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">cells</tok></cons></cons> <cons cat="VP"><tok cat="VBN">studied</tok> <cons cat="NP" null="NONE"></cons></cons></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">homozygous</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">wild-type</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" syn="COOD" role="PRD"><cons cat="ADJP"><tok cat="JJ">heterozygous</tok> <cons cat="PP" ref="i5" null="RNR"></cons></cons><cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="ADJP"><tok cat="JJ">homozygous</tok> <cons cat="PP" ref="i5" null="RNR"></cons></cons><cons cat="PP" id="i5"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">codon-10-variant</tok> <tok cat="NN">type</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1023547608@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">codon-10-variant</tok> <tok cat="NN">type</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">characteristic</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">breast</tok> <tok cat="NN">cancer</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1023547609@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="IN">Out</tok> <tok cat="JJ">current</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="JJ">further</tok> <tok cat="NNS">investigations</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">warranted</tok> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">elucidate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">possible</tok> <tok cat="NN">linkage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">ER</tok> <tok cat="NN">codon</tok> <tok cat="CD">10</tok> <tok cat="NN">polymorphism</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">physiological</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">pathological</tok></cons></cons> <tok cat="NNS">conditions</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1023550901@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">reactivation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">infected</tok> <tok cat="NNS">adults</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons> <tok cat="NN">CD4</tok> <tok cat="NN">cross-linking</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">ligands</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">CDR2-loop</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">extracellular</tok> <tok cat="NN">domain</tok> <tok cat="CD">1</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1023550902@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">HIV-1</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">infects</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">PBMCs</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBZ">remains</tok> <cons cat="NP" role="PRD"><tok cat="JJ">inactive</tok> <tok cat="NN">state</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">until</tok> <cons cat="NP"><tok cat="JJ">subsequent</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1023550903@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cross-linking</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">surface</tok> <tok cat="NN">CD4</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">gp120-anti-gp120</tok> <tok cat="JJ">immune</tok> <tok cat="NNS">complexes</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">heat-inactivated</tok> <tok cat="NN">HIV-1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">iHIV-1</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">sufficient</tok> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">trigger</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok> <tok cat="NNS">signals</tok></cons> <cons cat="VP"><tok cat="VBG">leading</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">virus</tok> <tok cat="NN">reactivation</tok> <tok cat="LRB">(</tok><tok cat="CD">9</tok><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1023550904@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i2" role="SBJ"><cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">stimulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">virus</tok> <tok cat="NN">production</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">iHIV-1</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">strictly</tok></cons> <cons cat="VP"><tok cat="VBN">linked</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">concentrations</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="JJ">exogenous</tok> <tok cat="NNS">stimuli</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1023550905@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="ADVP"><tok cat="RB">further</tok></cons> <cons cat="VP"><tok cat="VBD">investigated</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">physiologic</tok> <tok cat="NN">relevance</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">observations</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1023550906@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i3"><tok cat="WRB">When</tok></cons> <cons cat="S"><cons cat="NP" id="i4" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">submitted</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="FW">in</tok> <tok cat="FW">vitro</tok> <tok cat="NN">CD4</tok> <tok cat="NN">cross-linking</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">iHIV-1</tok></cons></cons><cons cat="ADVP" ref="i3" null="T"></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="NNS">PBMCs</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">HIV-1-infected</tok> <tok cat="NNS">patients</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">produce</tok> <cons cat="NP"><tok cat="NN">virus</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1023550907@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="DT">This</tok> <tok cat="JJ">viral</tok> <tok cat="NN">reactivation</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">patients</tok><tok cat="POS">'</tok> <tok cat="NNS">PBMCs</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1023550908@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Additionally</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><tok cat="NN">virus</tok> <tok cat="NN">reactivation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="NNS">PBMCs</tok></cons> <cons cat="VP"><tok cat="VBN">infected</tok> <cons cat="NP" null="NONE"></cons><cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="S"><cons cat="NP" ref="i7" id="i8" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADVP"><tok cat="RB">specifically</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><cons cat="NP"><tok cat="NNS">ligands</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">CDR2-loop</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">domain</tok> <tok cat="CD">1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">D1</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CD4</tok></cons></cons></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">virus</tok> <tok cat="NN">envelope</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">anti-CD4</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons><cons cat="NP" id="i9"><tok cat="JJ">monoclonal</tok> <tok cat="NNS">antibodies</tok></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1023550909@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i10" role="SBJ"><tok cat="NN">virus</tok> <tok cat="NN">reactivation</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP" adv="TMP"><tok cat="VBG">following</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD4</tok> <tok cat="NN">oligomerization</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">antibodies</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i11"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">bind</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="NNS">epitopes</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">D1</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">D1/CDR3-loop</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1023550910@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Finally</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">soluble</tok> <tok cat="NN">CD4</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">sCD4</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBD">prevented</tok> <cons cat="NP"><tok cat="NN">virus</tok> <tok cat="NN">reactivation</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">D1/CDR2-loop</tok> <tok cat="NNS">ligands</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1023550911@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">events</tok></cons> <cons cat="VP"><tok cat="VBN">initiated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">PBMCs</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">oligomerization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CD4</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">D1/CDR2-loop</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">trigger</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">HIV-1</tok> <tok cat="NN">upregulation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">infected</tok> <tok cat="NNS">individuals</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1031881401@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Bacterial</tok> <tok cat="NN">peptidoglycan</tok></cons> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">CD14-dependent</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CREB/ATF</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1031881402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Peptidoglycan</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">PGN</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">major</tok> <tok cat="NN">cell</tok> <tok cat="NN">wall</tok> <tok cat="NN">component</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">Gram-positive</tok> <tok cat="NNS">bacteria</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">secretion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">cytokines</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">macrophages</tok></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD14</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">pattern</tok> <tok cat="NN">recognition</tok> <tok cat="NN">receptor</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">binds</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">lipopolysaccharide</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">other</tok> <tok cat="JJ">microbial</tok> <tok cat="NNS">products</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1031881403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">begin</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">elucidate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">regulate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">wanted</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">determine</tok> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" id="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">PGN</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">mouse</tok> <tok cat="NN">RAW264.7</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">THP-1</tok> <tok cat="NN">macrophage</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1031881404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok><tok cat="COLON">:</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">i</tok><tok cat="RRB">)</tok></cons> <cons cat="NP" role="SBJ"><tok cat="NN">PGN</tok></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">ATF-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">CREB</tok></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok></cons> <cons cat="S"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">ii</tok><tok cat="RRB">)</tok></cons> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">ATF-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">CREB</tok></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">bound</tok> <cons cat="NP"><tok cat="NN">DNA</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">dimer</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">CRE</tok> <tok cat="NN">reporter</tok> <tok cat="NN">plasmid</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" id="i7" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><tok cat="JJ">dominant</tok> <tok cat="JJ">negative</tok> <cons cat="NP"><tok cat="NN">CREB</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">ATF-1</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok></cons> <cons cat="S"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">iii</tok><tok cat="RRB">)</tok></cons> <cons cat="NP" role="SBJ"><tok cat="NN">PGN</tok></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">c-Jun</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">protein</tok> <tok cat="NN">synthesis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">JunB</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">c-Fos</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">AP-1</tok> <tok cat="NN">reporter</tok> <tok cat="NN">plasmid</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i8"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i8" id="i9" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="JJ">dominant</tok> <tok cat="JJ">negative</tok> <tok cat="NN">c-Fos</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok></cons> <tok cat="CC">and</tok> <cons cat="S"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">iv</tok><tok cat="RRB">)</tok></cons> <cons cat="NP" id="i10" role="SBJ"><cons cat="NP"><tok cat="JJ">PGN-induced</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CREB/ATF</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="NN">CD14</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@98@@oe@16-12-2010 1031881405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">first</tok> <tok cat="NN">study</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i11" null="ZERO"></cons><cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">demonstrate</tok> <cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CREB/ATF</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok></cons></cons> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">PGN</tok></cons></cons> <tok cat="CC">or</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">any</tok> <tok cat="JJ">other</tok> <tok cat="NN">component</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">Gram-positive</tok> <tok cat="NNS">bacteria</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1031894201@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">Defining</tok> <cons cat="NP"><tok cat="JJ">therapeutic</tok> <tok cat="NNS">targets</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="NN">adenovirus</tok></cons></cons></cons></cons></cons><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="S" role="SBJ"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">blocking</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><tok cat="CC">both</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">inflammatory</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">destructive</tok></cons></cons> <tok cat="NNS">mechanisms</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">rheumatoid</tok> <tok cat="NN">synovium</tok></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBZ">spares</tok> <cons cat="NP"><tok cat="JJ">anti-inflammatory</tok> <tok cat="NNS">mediators</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1031894202@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">NF-kappaB</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">pathogenesis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">rheumatoid</tok> <tok cat="NN">arthritis</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="ADVP"><tok cat="RB">long</tok></cons> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">subject</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">controversy</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1031894203@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">used</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">adenoviral</tok> <tok cat="NN">technique</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">blocking</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">overexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">inhibitory</tok> <tok cat="NN">subunit</tok> <tok cat="NN">IkappaBalpha</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">advantage</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">diseased</tok> <tok cat="NN">tissue</tok></cons> <cons cat="NP"><tok cat="PRP">itself</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><cons cat="QP"><tok cat="JJR">></tok><tok cat="CD">90</tok></cons><tok cat="NN">%</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">synovial</tok> <tok cat="NNS">macrophages</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NNS">fibroblasts</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">infected</tok><cons cat="NP" null="NONE"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@47@@oe@16-12-2010 1031894204@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">spontaneous</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok> <tok cat="NN">alpha</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">other</tok> <tok cat="JJ">pro-inflammatory</tok> <tok cat="NNS">cytokines</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">NF-kappaB-dependent</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">rheumatoid</tok> <tok cat="JJ">synovial</tok> <tok cat="NN">tissue</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">contrast</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">main</tok> <tok cat="JJ">anti-inflammatory</tok> <tok cat="NNS">mediators</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">like</tok> <cons cat="NP" syn="COOD"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-10</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="CD">-11</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-1</tok> <tok cat="NN">receptor</tok> <tok cat="NN">antagonist</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1031894205@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Of</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="RB">even</tok> <tok cat="JJR">more</tok></cons> <tok cat="NN">interest</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">IkappaBalpha</tok> <tok cat="NN">overexpression</tok></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">matrix</tok> <tok cat="NNS">metalloproteinases</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="CD">3</tok></cons></cons></cons></cons></cons> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="RB">not</tok> <tok cat="VBG">affecting</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">tissue</tok> <tok cat="NN">inhibitor</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1031894206@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" role="SBJ"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">Blocking</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">rheumatoid</tok> <tok cat="NN">joint</tok></cons></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">thus</tok></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="RB">very</tok> <tok cat="JJ">beneficial</tok> <tok cat="NN">profile</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR" null="ZERO"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">reducing</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">inflammatory</tok> <tok cat="NN">response</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">tissue</tok> <tok cat="NN">destruction</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1031894207@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">adenoviral</tok> <tok cat="NN">technique</tok></cons> <cons cat="VP"><tok cat="VBN">described</tok> <cons cat="NP" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">here</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="NP"><tok cat="JJ">widespread</tok> <tok cat="NN">applicability</tok></cons><tok cat="COMMA">,</tok> <cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">allowing</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">rapid</tok> <tok cat="NN">testing</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">blocking</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">potential</tok> <tok cat="JJ">therapeutic</tok> <tok cat="NN">target</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="CC">either</tok> <tok cat="NNS">cultures</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">diseased</tok> <tok cat="NN">tissue</tok></cons> <cons cat="NP"><tok cat="PRP">itself</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1032036701@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Nuclear</tok> <tok cat="NN">factor-90</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">activated</tok> <tok cat="NNS">T-cells</tok></cons></cons><tok cat="COLON">:</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="JJ">double-stranded</tok> <tok cat="JJ">RNA-binding</tok> <tok cat="NN">protein</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">substrate</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">double-stranded</tok> <tok cat="JJ">RNA-dependent</tok> <tok cat="NN">protein</tok> <tok cat="NN">kinase</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">PKR</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1032036702@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NFAT</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="VP"><tok cat="VBP">play</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">central</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">initiating</tok> <cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">immediate-early</tok> <tok cat="NN">T-cell</tok> <tok cat="JJ">specific</tok> <tok cat="NNS">genes</tok></cons> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin-2</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-2</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1032036703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NFAT</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="VP"><tok cat="VBP">bind</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">sequence</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">enhancer</tok></cons> <cons cat="ADJP"><tok cat="VBN">known</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">antigen</tok> <tok cat="NN">receptor</tok> <tok cat="NN">response</tok> <tok cat="NN">element</tok> <tok cat="CD">2</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">ARRE-2</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1032036704@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="JJ">Multiple</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="VP"><tok cat="VBG">exhibiting</tok> <cons cat="NP"><tok cat="NN">ARRE-2</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">isolated</tok><cons cat="NP" ref="i1" null="NONE"></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">heterodimer</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">stimulated</tok> <tok cat="NN">T-cell</tok> <tok cat="JJ">nuclear</tok> <tok cat="NNS">extracts</tok></cons> <cons cat="VP"><tok cat="VBG">consisting</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Mr</tok></cons> <cons cat="VP"><tok cat="JJ">=</tok> <cons cat="NP" role="PRD"><tok cat="CD">90</tok> <tok cat="CD">000</tok></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NF90</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Mr</tok></cons> <cons cat="VP"><tok cat="JJ">=</tok> <cons cat="NP" role="PRD"><tok cat="CD">45</tok> <tok cat="CD">000</tok></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NF45</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <tok cat="NNS">subunits</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1032036705@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NNS">subunits</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">heterodimer</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">cloned</tok><cons cat="NP" ref="i2" null="NONE"></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="NN">NF90</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i3" id="i4" null="NONE"></cons><cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">encode</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">protein</tok></cons> <cons cat="VP"><tok cat="VBG">containing</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">two</tok> <tok cat="NNS">domains</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" id="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">predicted</tok> <cons cat="NP" ref="i6" id="i7" null="NONE"></cons><cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">form</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">motifs</tok></cons> <cons cat="ADJP"><tok cat="JJ">capable</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">binding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">double-stranded</tok> <tok cat="NN">RNA</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1032036706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">Using</tok> <cons cat="NP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok> <tok cat="VBN">translated</tok> <tok cat="NNS">polypeptides</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NF90</tok></cons> <cons cat="ADVP"><tok cat="RB">specifically</tok></cons> <cons cat="VP"><tok cat="VBZ">binds</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">double-stranded</tok> <tok cat="NN">RNA</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1032036707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i8" role="SBJ"><tok cat="NN">NF90</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">phosphorylated</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">double-stranded</tok> <tok cat="JJ">RNA-dependent</tok> <tok cat="NN">manner</tok></cons></cons> <cons cat="PP"><cons cat="ADVP"><tok cat="RB">likely</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">interferon-induced</tok><tok cat="COMMA">,</tok> <tok cat="JJ">double-stranded</tok> <tok cat="JJ">RNA-dependent</tok> <tok cat="NN">protein</tok> <tok cat="NN">kinase</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">PKR</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1032036708@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i9" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">NF90</tok> <tok cat="NN">protein</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i9" id="i10" null="NONE"></cons><cons cat="S"><cons cat="NP" ref="i10" id="i11" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="CONJP"><tok cat="RB">not</tok> <tok cat="RB">only</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">T-cells</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="CONJP"><tok cat="CC">but</tok> <tok cat="RB">also</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">nonimmune</tok> <tok cat="NN">HeLa</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1032036709@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">HeLa</tok> <tok cat="NNS">cells</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i12" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">protein</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">almost</tok> <tok cat="RB">exclusively</tok></cons> <cons cat="VP"><tok cat="JJ">localized</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ribosome</tok> <tok cat="NN">salt</tok> <tok cat="NN">wash</tok> <tok cat="NN">fraction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NNS">lysates</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1032216001@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">lymphocyte</tok> <tok cat="NN">development</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Ikaros</tok> <tok cat="NN">gene</tok> <tok cat="NN">family</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@10@@oe@16-12-2010 1032216002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Lymphoid</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="VP"><tok cat="VBZ">relies</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP" syn="COOD"><cons cat="ADJP"><tok cat="RB">precisely</tok> <tok cat="VBN">orchestrated</tok></cons> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">activation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">repression</tok> <tok cat="NNS">events</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1032216003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Gene</tok> <tok cat="NN">targeting</tok> <tok cat="NNS">studies</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">demonstrated</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">crucial</tok> <tok cat="NNS">roles</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Ikaros</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Aiolos</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">regulating</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">multiple</tok> <tok cat="NNS">stages</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">B</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">T</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NN">cell</tok> <tok cat="NN">development</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1032216004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Recent</tok> <tok cat="NNS">experiments</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">Ikaros</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Aiolos</tok></cons></cons> <cons cat="VP"><tok cat="VBP">set</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="NN">B</tok> <tok cat="NN">cell</tok> <tok cat="NN">antigen-receptor</tok> <tok cat="LRB">(</tok><tok cat="NN">BCR</tok><tok cat="RRB">)</tok><tok cat="COLON">-</tok> <cons cat="ADJP" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">TCR-mediated</tok></cons></cons> <cons cat="NP"><tok cat="NN">signaling</tok> <tok cat="NNS">thresholds</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NNS">molecules</tok></cons> <cons cat="VP"><tok cat="VBP">exist</tok> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NNS">complexes</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">contain</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">nucleosome</tok> <tok cat="NN">remodeling</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">histone</tok> <tok cat="NN">deacetylase</tok> <tok cat="NNS">activities</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@39@@oe@16-12-2010 1032705001@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Cell</tok> <tok cat="JJ">growth-regulated</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><tok cat="JJ">mammalian</tok> <cons cat="NP"><tok cat="NN">MCM5</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">MCM6</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NNS">genes</tok></cons></cons> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">E2F</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1032705002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Initiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NN">replication</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">requires</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">function</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">MCM</tok> <tok cat="NN">gene</tok> <tok cat="NNS">products</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">participate</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">ensuring</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">DNA</tok> <tok cat="NN">replication</tok></cons> <cons cat="VP"><tok cat="VBZ">occurs</tok> <cons cat="ADVP"><tok cat="RB">only</tok> <tok cat="RB">once</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cell</tok> <tok cat="NN">cycle</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1032705003@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">Expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">all</tok> <tok cat="JJ">mammalian</tok> <tok cat="NNS">genes</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">MCM</tok> <tok cat="NN">family</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">growth</tok> <tok cat="NN">stimulation</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">unlike</tok> <cons cat="NP"><tok cat="NN">yeast</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">mRNA</tok> <tok cat="NNS">levels</tok></cons> <cons cat="VP"><tok cat="VBP">peak</tok> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="NN">G1/S</tok> <tok cat="NN">boundary</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1032705004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">examined</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NNS">activities</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">isolated</tok> <tok cat="JJ">human</tok> <tok cat="NN">MCM</tok> <tok cat="NN">gene</tok> <tok cat="NNS">promoters</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1032705005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Human</tok> <tok cat="NN">MCM5</tok> <tok cat="CC">and</tok> <tok cat="NN">MCM6</tok> <tok cat="NNS">promoters</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">mutation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">E2F</tok> <tok cat="NNS">sites</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">failed</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">promoter</tok> <tok cat="NN">regulation</tok></cons> <cons cat="VP"><tok cat="VBG">following</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">serum</tok> <tok cat="NN">stimulation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">exogenous</tok> <tok cat="NN">E2F</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1032705006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">identified</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="JJ">E2F-like</tok> <tok cat="NN">sequence</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">MCM6</tok> <tok cat="NN">promoter</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">cooperates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">authentic</tok> <tok cat="NN">E2F</tok> <tok cat="NNS">sites</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">E2F-dependent</tok> <tok cat="NN">regulation</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1032705007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Forced</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">E2F1</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">could</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">all</tok> <tok cat="NNS">members</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">endogenous</tok> <tok cat="NN">MCM</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">rat</tok> <tok cat="JJ">embryonal</tok> <tok cat="NN">fibroblast</tok> <tok cat="NN">REF52</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1032705008@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">growth-regulated</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP" syn="COOD"><tok cat="JJ">mammalian</tok> <cons cat="NP"><tok cat="NN">MCM5</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">MCM6</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><cons cat="NP" id="i5"><tok cat="NNS">genes</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">presumably</tok></cons> <cons cat="NP"><tok cat="JJ">other</tok> <tok cat="NN">MCM</tok> <tok cat="NNS">members</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">primarily</tok></cons> <cons cat="VP"><tok cat="VBN">regulated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">E2F</tok></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="NN">binding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">multiple</tok> <tok cat="NN">E2F</tok> <tok cat="NNS">sites</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">promoters</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1032706401@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="ADJP"><tok cat="NN">c-Myc</tok> <tok cat="CC">and</tok> <tok cat="NN">E1A</tok> <tok cat="JJ">induced</tok></cons> <tok cat="JJ">cellular</tok> <tok cat="NN">sensitivity</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="VBN">activated</tok> <tok cat="NN">NK</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">involves</tok> <cons cat="NP"><tok cat="JJ">cytotoxic</tok> <tok cat="NNS">granules</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="NN">death</tok> <tok cat="NNS">effectors</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1032706402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">contact</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">natural</tok> <tok cat="NN">killer</tok> <tok cat="LRB">(</tok><tok cat="NN">NK</tok><tok cat="RRB">)</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">foreign</tok> <tok cat="NNS">cells</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><tok cat="JJ">certain</tok> <cons cat="NP"><tok cat="JJ">virus-infected</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">tumor</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NNS">cells</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">triggers</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cytolytic</tok> <tok cat="NN">machinery</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NK</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1032706403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">triggering</tok></cons> <cons cat="VP"><tok cat="VBZ">leads</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">exocytosis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cytotoxic</tok> <tok cat="NN">NK</tok> <tok cat="NN">cell</tok> <tok cat="NNS">granules</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1032706404@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="NNS">oncoproteins</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">c-Myc</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">E1A</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">render</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NNS">cells</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">vulnerable</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">NK</tok> <tok cat="NN">cell</tok> <tok cat="JJ">mediated</tok> <tok cat="NN">cytolysis</tok></cons></cons></cons></cons></cons></cons> <tok cat="RB">yet</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">sensitization</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <tok cat="RB">not</tok> <cons cat="ADVP"><tok cat="RB">well</tok></cons> <cons cat="VP"><tok cat="VBN">understood</tok><cons cat="NP" ref="i2" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1032706405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">model</tok> <tok cat="WRB">where</tok> <tok cat="JJ">foreign</tok> <tok cat="NNS">cells</tok> <tok cat="LRB">(</tok><tok cat="NN">rat</tok> <tok cat="NNS">fibroblasts</tok><tok cat="RRB">)</tok> <tok cat="VBD">were</tok> <tok cat="VBN">cocultured</tok> <tok cat="IN">with</tok> <tok cat="JJ">human</tok> <tok cat="NN">IL-2</tok> <tok cat="JJ">activated</tok> <tok cat="NN">NK</tok> <tok cat="NNS">cells</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">observed</tok> <tok cat="IN">that</tok> <tok cat="NN">NK</tok> <tok cat="NNS">cells</tok> <tok cat="VBD">were</tok> <tok cat="JJ">capable</tok> <tok cat="IN">of</tok> <tok cat="RB">efficiently</tok> <tok cat="VBG">killing</tok> <tok cat="PRPP">their</tok> <tok cat="NNS">targets</tok> <tok cat="RB">only</tok> <tok cat="IN">if</tok> <tok cat="DT">the</tok> <tok cat="NNS">cells</tok> <tok cat="VBD">overexpressed</tok> <tok cat="DT">the</tok> <tok cat="NN">oncogene</tok> <tok cat="NN">c-Myc</tok> <tok cat="CC">or</tok> <tok cat="NN">E1A</tok></cons><tok cat="PERIOD">.</tok></cons>@@@@1@42@@oe@16-12-2010 1032706406@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><tok cat="CC">Both</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">parental</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">oncogene</tok> <tok cat="NN">expressing</tok> <tok cat="NNS">fibroblasts</tok></cons></cons> <cons cat="ADVP"><tok cat="RB">similarly</tok></cons> <cons cat="VP"><tok cat="VBD">triggered</tok> <cons cat="NP"><tok cat="NN">phosphoinositide</tok> <tok cat="NN">hydrolysis</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">bound</tok> <tok cat="NN">NK</tok> <tok cat="NNS">cells</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">demonstrating</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="NN">NK</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">cytolytically</tok></cons> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">contact</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="JJ">resistant</tok> <tok cat="JJ">parental</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">oncogene</tok> <tok cat="NN">expressing</tok> <tok cat="JJ">sensitive</tok> <tok cat="NN">target</tok> <tok cat="NNS">fibroblasts</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1032706407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">cell</tok> <tok cat="NN">death</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">independent</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">wild-type</tok> <tok cat="NN">p53</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">an</tok> <tok cat="JJ">anti-apoptotic</tok> <tok cat="NN">protein</tok> <tok cat="NN">EIB19K</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1032706408@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBD">provided</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">evidence</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">c-Myc</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">E1A</tok></cons></cons> <cons cat="VP"><tok cat="VBD">activated</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NK</tok> <tok cat="NN">cell</tok> <tok cat="JJ">induced</tok> <tok cat="NN">cytolysis</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">post-triggering</tok> <tok cat="NN">stage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NK</tok> <tok cat="JJ">cell-target</tok> <tok cat="NN">cell</tok> <tok cat="NN">interaction</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1032706409@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">consistence</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="ADJP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">c-Myc</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">E1A</tok></cons></cons> <tok cat="NN">overexpressing</tok></cons> <tok cat="NNS">fibroblasts</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><cons cat="ADJP"><tok cat="RBR">more</tok> <tok cat="JJ">sensitive</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cytolytic</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">isolated</tok> <tok cat="NN">NK</tok> <tok cat="JJ">cell-derived</tok> <tok cat="NNS">granules</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><tok cat="JJ">parental</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1032706410@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NNS">oncogenes</tok></cons> <cons cat="VP"><tok cat="VBP">activate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cytotoxicity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NK</tok> <tok cat="NN">cell</tok> <tok cat="NNS">granules</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1032706411@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">mechanism</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">have</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">directing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cytolytic</tok> <tok cat="NN">action</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NK</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">towards</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">virus-infected</tok> <tok cat="CC">and</tok> <tok cat="NN">cancer</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1032810701@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Apoptosis</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">growth</tok> <tok cat="NN">inhibition</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">malignant</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">treatment</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">arsenic</tok> <tok cat="NN">trioxide</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="RB">clinically</tok> <tok cat="JJ">achievable</tok></cons> <tok cat="NNS">concentrations</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">[</tok><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VB">see</tok> <cons cat="NP"><tok cat="NNS">comments</tok></cons></cons></cons><tok cat="RRB">]</tok></cons></cons>@@@@1@20@@oe@16-12-2010 1032810702@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">BACKGROUND</tok><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Arsenic</tok> <tok cat="NN">trioxide</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">As2O3</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">clinical</tok> <tok cat="NN">remission</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">acute</tok> <tok cat="JJ">promyelocytic</tok> <tok cat="NN">leukemia</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">differentiation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">programmed</tok> <tok cat="NN">cell</tok> <tok cat="NN">death</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">apoptosis</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1032810703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">investigated</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">As2O3</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">panel</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">malignant</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">determine</tok> <cons cat="SBAR"><tok cat="IN">whether</tok> <cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">growth-inhibitory</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">apoptotic</tok></cons></cons> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">As2O3</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="RB">clinically</tok> <tok cat="JJ">achievable</tok></cons> <tok cat="NNS">concentrations</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1032810704@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NNS">METHODS</tok><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" syn="COOD" id="i2" role="SBJ"><cons cat="NP"><tok cat="CD">Eight</tok> <tok cat="JJ">malignant</tok> <tok cat="JJ">lymphocytic</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">primary</tok> <tok cat="NNS">cultures</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">lymphocytic</tok> <tok cat="NN">leukemia</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">lymphoma</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><cons cat="NP" id="i3"><tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">treated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">As2O3</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><cons cat="NP" syn="COOD" id="i4"><cons cat="NP"><cons cat="NP"><tok cat="NN">dithiothreitol</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">DTT</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">buthionine</tok> <tok cat="NN">sulfoximine</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">BSO</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">glutathione</tok> <tok cat="NN">synthesis</tok></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@42@@oe@16-12-2010 1032810705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NN">Apoptosis</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">assessed</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">morphology</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">flow</tok> <tok cat="NN">cytometry</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">annexin</tok> <tok cat="NN">V</tok> <tok cat="NN">protein</tok> <tok cat="NN">level</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">terminal</tok> <tok cat="NN">deoxynucleotidyl</tok> <tok cat="NN">transferase</tok> <tok cat="NN">labeling</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NNS">fragments</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1032810706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="JJ">Cellular</tok> <tok cat="NN">proliferation</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">determined</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><cons cat="NP"><tok cat="NN">5-bromo-2'-deoxyuridine</tok> <tok cat="NN">incorporation</tok> <tok cat="IN">into</tok> <tok cat="NN">DNA</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">flow</tok> <tok cat="NN">cytometry</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">use</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">mitotic</tok> <tok cat="NN">arrest</tok> <tok cat="NN">assay</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1032810707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="JJ">Mitochondrial</tok> <tok cat="JJ">transmembrane</tok> <tok cat="NN">potential</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">delta</tok> <tok cat="NN">psi(m)</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">measured</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">means</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">rhodamine</tok> <tok cat="CD">123</tok> <tok cat="NN">staining</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">flow</tok> <tok cat="NN">cytometry</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1032810708@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="NN">Protein</tok> <tok cat="NN">expression</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">assessed</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><cons cat="NP"><tok cat="NN">western</tok> <tok cat="NN">blot</tok> <tok cat="NN">analysis</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">immunofluorescence</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1032810709@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NNS">RESULTS</tok><tok cat="COLON">:</tok></cons> <cons cat="NP"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Therapeutic</tok> <tok cat="NNS">concentrations</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">As2O3</tok></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="QP"><tok cat="CD">1-2</tok></cons> <tok cat="NN">microM</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><tok cat="JJ">dual</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">malignant</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons><tok cat="COLON">:</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP" syn="COOD"><cons cat="LST"><tok cat="LS">1</tok><tok cat="RRB">)</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">growth</tok></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="NN">adenosine</tok> <tok cat="NN">triphosphate</tok> <tok cat="LRB">(</tok><tok cat="NN">ATP</tok><tok cat="RRB">)</tok> <tok cat="NN">depletion</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">prolongation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">cycle</tok> <tok cat="NN">time</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="LST"><tok cat="LS">2</tok><tok cat="RRB">)</tok></cons> <cons cat="NP"><tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@42@@oe@16-12-2010 1032810710@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">As2O3-induced</tok> <tok cat="NN">apoptosis</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">preceded</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">delta</tok> <tok cat="NN">psi(m)</tok> <tok cat="NN">collapse</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@9@@oe@16-12-2010 1032810711@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">DTT</tok></cons> <cons cat="VP"><tok cat="VBD">antagonized</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons></cons><tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">BSO</tok></cons> <cons cat="VP"><tok cat="VBD">enhanced</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons></cons><cons cat="NP" syn="COOD" id="i9"><cons cat="NP"><tok cat="JJ">As2O3-induced</tok> <tok cat="NN">ATP</tok> <tok cat="NN">depletion</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">delta</tok> <tok cat="NN">psi(m)</tok> <tok cat="NN">collapse</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1032810712@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i10" role="SBJ"><cons cat="NP"><tok cat="NN">Caspase-3</tok> <tok cat="NN">activation</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">usually</tok></cons> <tok cat="VBG">resulting</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">delta</tok> <tok cat="NN">psi(m)</tok> <tok cat="NN">collapse</tok></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="ADVP"><tok cat="RB">always</tok></cons> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">As2O3-induced</tok> <tok cat="NN">apoptosis</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1032810713@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">As2O3</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">PML</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="JJ">promyelocytic</tok> <tok cat="NN">leukemia</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">protein</tok> <tok cat="NN">degradation</tok></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">modulate</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cell</tok> <tok cat="JJ">cycle-related</tok> <tok cat="NNS">proteins</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">c-myc</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">retinoblastoma</tok> <tok cat="NN">protein</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">cyclin-dependent</tok> <tok cat="NN">kinase</tok> <tok cat="CD">4</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">cyclin</tok> <tok cat="NN">D1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">p53</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">differentiation-related</tok> <tok cat="NNS">antigens</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1032810714@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NNS">CONCLUSIONS</tok><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" syn="COOD" id="i11" role="SBJ"><cons cat="NP"><tok cat="JJ">Substantial</tok> <tok cat="NN">growth</tok> <tok cat="NN">inhibition</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">apoptosis</tok></cons> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">evidence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJS">most</tok> <tok cat="JJ">malignant</tok> <tok cat="JJ">lymphocytic</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">treated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="QP"><tok cat="CD">1-2</tok></cons> <tok cat="NN">microM</tok> <tok cat="NN">As2O3</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1032810715@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">As2O3</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">prove</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">useful</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">treatment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">malignant</tok> <tok cat="JJ">lymphoproliferative</tok> <tok cat="NNS">disorders</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1032887401@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Non-steroidal</tok> <tok cat="JJ">anti-inflammatory</tok> <tok cat="NNS">drugs</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">inhibit</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">cytokines</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">induce</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">HSP70</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1032887402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Recent</tok> <tok cat="NNS">studies</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">non-steroidal</tok> <tok cat="JJ">anti-inflammatory</tok> <tok cat="NNS">drugs</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">NSAIDs</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBP">activate</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">heat</tok> <tok cat="NN">shock</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">HSF1</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">latent</tok> <tok cat="JJ">cytoplasmic</tok> <tok cat="NN">form</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">nuclear</tok><tok cat="COMMA">,</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">state</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1032887403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">As</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">HSF1</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="NN">function</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">activator</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">heat</tok> <tok cat="NN">shock</tok> <tok cat="NNS">genes</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">repressor</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">non-heat</tok> <tok cat="NN">shock</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL1B</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">c- fos</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">examined</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">potential</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HSF1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">NSAIDs</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">human</tok> <tok cat="JJ">monocytic</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok> <tok cat="NN">THP-1</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@49@@oe@16-12-2010 1032887404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="CD">two</tok> <tok cat="NNS">members</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">NSAIDs</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">sodium</tok> <tok cat="NN">salicylate</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">sulindac</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">repress</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL1B</tok> <tok cat="NN">promoter</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">similar</tok> <tok cat="NN">degree</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">heat</tok> <tok cat="NN">shock</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">HSF1</tok> <tok cat="NN">overexpression</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1032887405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">sodium</tok> <tok cat="NN">salicylate</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">additional</tok> <tok cat="NNS">NSAIDs</tok></cons></cons> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">concentrations</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">activate</tok> <cons cat="NP"><tok cat="NN">HSF1</tok></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="JJ">monocytic</tok> <tok cat="NNS">genes</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-1beta</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-6</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-8</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">ICAM-1</tok></cons></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">exposure</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">pro-inflammatory</tok> <tok cat="NN">stimulus</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="NN">lipopolysaccharide</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">LPS</tok></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@48@@oe@16-12-2010 1032887406@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><cons cat="ADVP"><tok cat="IN">At</tok> <tok cat="JJS">least</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">case</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL1B</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="NN">repression</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">seem</tok> <cons cat="S"><cons cat="NP" ref="i8" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">involve</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">another</tok> <tok cat="NN">factor</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i9"><tok cat="WPP">whose</tok> <tok cat="NN">activity</tok></cons> <cons cat="S"><cons cat="NP" ref="i9" id="i10" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">affected</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">the</tok> <tok cat="NNS">NSAIDs</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">NFkappaB</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL1B</tok> <tok cat="NN">promoter</tok> <tok cat="NN">fragment</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="PRPP">our</tok> <tok cat="NNS">studies</tok></cons></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="ADJP" role="PRD"><tok cat="NN">NFkappaB</tok> <tok cat="JJ">responsive</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">binds</tok> <cons cat="ADVP"><tok cat="RB">specifically</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">HSF1</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@46@@oe@16-12-2010 1032887407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Exposure</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NNS">NSAIDs</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">complex</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">HSP</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">sulindac</tok></cons> <cons cat="VP" id="i2"><tok cat="VBD">activated</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">stress</tok> <tok cat="JJ">responsive</tok> <tok cat="NN">HSP70B</tok> <tok cat="NN">promoter</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">sodium</tok> <tok cat="NN">salicylate</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok><cons cat="VP" ref="i2" null="QSTN"></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1032887408@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="ADVP"><tok cat="RB">only</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">subset</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NSAIDs</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><tok cat="NN">HSP70</tok> <tok cat="NN">mRNA</tok> <tok cat="NNS">species</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1032887409@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">reflect</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">properties</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">HSF1</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" id="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><cons cat="QP"><tok cat="IN">at</tok> <tok cat="JJS">least</tok> <tok cat="CD">two</tok></cons> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NNS">forms</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><cons cat="NP"><cons cat="ADVP"><tok cat="RB">only</tok></cons> <cons cat="NP"><tok cat="CD">one</tok></cons></cons> <cons cat="WHPP"><tok cat="IN">of</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">activates</tok> <cons cat="NP"><tok cat="NN">heat</tok> <tok cat="NN">shock</tok> <tok cat="NNS">promoters</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">individual</tok> <tok cat="NN">NSAID</tok> <tok cat="NN">family</tok> <tok cat="NNS">members</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="ADVP"><tok cat="RB">differentially</tok></cons> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="CD">one</tok></cons> <cons cat="PP" ref="i6" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok></cons> <cons cat="PP" ref="i6" null="RNR"></cons></cons></cons><cons cat="PP" id="i6"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">forms</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1032887410@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="ADVP"><tok cat="RB">Overall</tok> <tok cat="RB">therefore</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">exposure</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NNS">NSAIDs</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">leads</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">profound</tok> <tok cat="NN">switch</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">monocytic</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">suppression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">genes</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">macrophage</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">stress</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="NN">HSF1</tok></cons> <cons cat="VP"><tok cat="VBZ">appears</tok> <cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">play</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">effects</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1032887411@GENIA Treebank@formal@@1@S@<cons cat="NP"><tok cat="NN">Copyright</tok> <tok cat="CD">1999</tok> <tok cat="NNP">Academic</tok> <tok cat="NNP">Press</tok><tok cat="PERIOD">.</tok></cons>@@@@1@5@@oe@16-12-2010 1032914701@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Recognition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NFATp/AP-1</tok> <tok cat="JJ">composite</tok> <tok cat="NNS">elements</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">genes</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">immune</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1032914702@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Composite</tok> <tok cat="NNS">elements</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP" role="PRD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">regulatory</tok> <tok cat="NNS">modules</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">promoters</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NNS">enhancers</tok></cons></cons></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">consist</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBG">binding</tok> <tok cat="NNS">sites</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="CD">two</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">different</tok></cons> <tok cat="CC">but</tok> <cons cat="ADJP"><tok cat="VBG">synergizing</tok></cons></cons> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1032914703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">A</tok> <tok cat="JJ">well-studied</tok> <tok cat="NN">example</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NNS">factors</tok> <tok cat="IN">of</tok> <tok cat="VBN">activated</tok> <tok cat="NN">T-cell</tok> <tok cat="LRB">(</tok><tok cat="NN">NFAT</tok><tok cat="RRB">)</tok> <tok cat="NNS">sites</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP"><tok cat="JJ">composite</tok> <tok cat="NNS">elements</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">NFATp/c</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">an</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBG">activating</tok> <tok cat="NN">protein</tok> <tok cat="CD">1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">AP-1</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">binding</tok> <tok cat="NN">site</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1032914704@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">developed</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">computational</tok> <tok cat="NN">approach</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">identify</tok> <cons cat="NP"><tok cat="JJ">potential</tok> <tok cat="NN">NFAT</tok> <tok cat="NN">target</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">which</tok></cons> <cons cat="S" syn="COOD"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">a</tok><tok cat="RRB">)</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">comprises</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">improved</tok> <tok cat="NN">method</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">scan</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">individual</tok> <tok cat="NN">NFAT</tok> <tok cat="JJ">composite</tok> <tok cat="NNS">elements</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">b</tok><tok cat="RRB">)</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">considers</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">positional</tok> <tok cat="NNS">effects</tok></cons> <cons cat="ADJP"><tok cat="JJ">relative</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">start</tok> <tok cat="NNS">sites</tok></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <tok cat="CC">and</tok> <cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">c</tok><tok cat="RRB">)</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">involves</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cluster</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">potential</tok> <tok cat="NN">NFAT</tok> <tok cat="JJ">composite</tok> <tok cat="NNS">elements</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@53@@oe@16-12-2010 1032914705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">All</tok> <tok cat="CD">three</tok> <tok cat="NNS">steps</tok></cons> <cons cat="ADVP"><tok cat="RB">progressively</tok></cons> <cons cat="VP"><tok cat="VBD">helpX?ed</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">discriminate</tok> <cons cat="NP"><tok cat="JJ">T-cell-specific</tok> <tok cat="NN">promoter</tok> <tok cat="NNS">sequences</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="JJ">functional</tok> <tok cat="NNS">regions</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">coding</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">intronic</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons></cons><cons cat="NP" id="i4"><tok cat="NNS">sequences</tok></cons></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">same</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">promoters</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">muscle-specific</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP"><tok cat="JJ">random</tok> <tok cat="NNS">sequences</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1032914706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">Using</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">approach</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">identified</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">potential</tok> <tok cat="NN">NFAT</tok> <tok cat="JJ">composite</tok> <tok cat="NNS">elements</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">promoters</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NNS">receptors</tok></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">promoters</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">genes</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">AP-1</tok> <tok cat="NN">family</tok> <tok cat="NNS">members</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">Ca2+-binding</tok> <tok cat="NNS">proteins</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">some</tok> <tok cat="JJ">other</tok> <tok cat="NNS">components</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">network</tok></cons> <cons cat="VP"><tok cat="VBG">operating</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="VBN">activated</tok> <tok cat="NNS">T-cells</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">other</tok> <tok cat="JJ">immune</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@49@@oe@16-12-2010 1032914707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">method</tok></cons> <cons cat="VP"><tok cat="VBN">developed</tok> <cons cat="NP" null="NONE"></cons></cons></cons><cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">adapted</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">characterize</tok> <cons cat="NP" ref="i7" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><tok cat="VB">identify</tok> <cons cat="NP" ref="i7" null="RNR"></cons></cons><cons cat="NP" id="i7"><tok cat="JJ">other</tok> <tok cat="JJ">composite</tok> <tok cat="NNS">elements</tok></cons> <cons cat="ADVP"><tok cat="RB">as</tok> <tok cat="RB">well</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1032914708@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">program</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">recognition</tok> <tok cat="NN">NFAT</tok> <tok cat="JJ">composite</tok> <tok cat="NNS">elements</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">available</tok> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">World</tok> <tok cat="NN">Wide</tok> <tok cat="NN">Web</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">http://compel.bionet.nsc.ru/FunSite/CompelScan.html</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">http://transfac.gbf.de/dbsearch/funsitep/s_comp.html</tok></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1032914709@GENIA Treebank@formal@@1@S@<cons cat="NP"><tok cat="NN">Copyright</tok> <tok cat="CD">1999</tok> <tok cat="NNP">Academic</tok> <tok cat="NNP">Press</tok><tok cat="PERIOD">.</tok></cons>@@@@1@5@@oe@16-12-2010 1032962501@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Disruption</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">alpha</tok> <tok cat="NN">beta</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons></cons><tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gamma</tok> <tok cat="NN">delta</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons></cons><cons cat="NP" id="i8"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">development</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">overexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">helix-loop-helix</tok> <tok cat="NN">protein</tok></cons> <cons cat="NP"><tok cat="NN">Id3</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="VBN">committed</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NNS">progenitors</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1032962502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="VBN">Enforced</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Id3</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">capacity</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">inhibit</tok> <cons cat="NP"><tok cat="JJ">many</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">basic</tok> <tok cat="JJ">helix-loop-helix</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="JJ">bHLH</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">CD34(+)</tok> <tok cat="JJ">hematopoietic</tok> <tok cat="NN">progenitor</tok> <tok cat="NNS">cells</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">have</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">undergone</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">TCR</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">gene</tok> <tok cat="NNS">rearrangements</tok></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">development</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">transduced</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">TCRalpha</tok> <tok cat="NN">beta</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">gamma</tok> <tok cat="NN">delta</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><cons cat="NP" id="i3"><tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <cons cat="NP"><tok cat="JJ">fetal</tok> <tok cat="JJ">thymic</tok> <tok cat="NN">organ</tok> <tok cat="NN">culture</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">FTOC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@61@@oe@16-12-2010 1032962503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">document</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">overexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Id3</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">progenitors</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">initiated</tok> <cons cat="NP"><tok cat="NN">TCR</tok> <tok cat="NN">gene</tok> <tok cat="NNS">rearrangements</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="JJ">pre-T</tok> <tok cat="NNS">cells</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">development</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="NN">TCRalpha</tok> <tok cat="NN">beta</tok></cons></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="NN">TCRgamma</tok> <tok cat="NN">delta</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1032962504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">Id3</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">impedes</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">recombination</tok> <tok cat="NN">activating</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">downregulates</tok> <cons cat="NP"><tok cat="JJ">pre-Talpha</tok> <tok cat="NN">mRNA</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1032962505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">observations</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">possible</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i5"><tok cat="IN">by</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Id3</tok> <tok cat="NN">overexpression</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="ADVP"><tok cat="RB">differentially</tok></cons> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">development</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">pre-T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">TCRalpha</tok> <tok cat="NN">beta</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">gamma</tok> <tok cat="NN">delta</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><cons cat="NP" id="i6"><tok cat="NNS">cells</tok></cons></cons></cons></cons><cons cat="PP" ref="i5" null="T"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1032962506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBD">observed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">surface</tok> <tok cat="JJ">CD4(-)CD8(-)CD3(-)</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="VBN">rearranged</tok> <tok cat="NN">TCR</tok> <tok cat="NNS">genes</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">developed</tok> <cons cat="PP"><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">Id3-transduced</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons></cons><tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">control-transduced</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons></cons><cons cat="NP" id="i9"><tok cat="JJ">pre-T</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">FTOC</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1032962507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">properties</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">natural</tok> <tok cat="NN">killer</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NK</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">pre-T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1032962508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="JJ">bHLH</tok> <tok cat="NNS">factors</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">control</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">development</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">T/NK</tok> <tok cat="JJ">developmental</tok> <tok cat="NN">checkpoint</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1032962601@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="NN">Rel/NF-kappaB</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">trigger</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Notch</tok> <tok cat="NN">signaling</tok> <tok cat="NN">pathway</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">inducing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Jagged1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">ligand</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">Notch</tok> <tok cat="NNS">receptors</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1032962602@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Jagged1</tok></cons> <cons cat="VP"><tok cat="VBZ">belongs</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">DSL</tok> <tok cat="NN">family</tok> <tok cat="IN">of</tok> <tok cat="NNS">ligands</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Notch</tok> <tok cat="NNS">receptors</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">control</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">proliferation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">differentiation</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">various</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lineages</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1032962603@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i4" role="SBJ"><tok cat="JJ">little</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">about</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">regulate</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1032962604@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Jagged1</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><tok cat="DT">a</tok> <tok cat="JJ">Rel/NF-kappaB-responsive</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1032962605@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><tok cat="CC">Both</tok> <cons cat="NP"><tok cat="NN">c-Rel</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">RelA</tok></cons></cons> <cons cat="VP" id="i14"><tok cat="VBD">induced</tok> <cons cat="NP"><tok cat="NN">jagged1</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">mutant</tok> <tok cat="JJ">defective</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">transactivation</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok><cons cat="VP" ref="i14" null="QSTN"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1032962606@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="ADVP"><tok cat="RB">Importantly</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="NN">jagged1</tok> <tok cat="NNS">transcripts</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">upregulated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="JJ">endogenous</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="DT">this</tok> <tok cat="NN">effect</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dominant</tok> <tok cat="NN">mutant</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IkappaBalpha</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">physiological</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1032962607@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Cell</tok> <tok cat="NN">surface</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Jagged1</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">c-Rel-expressing</tok> <tok cat="NN">cell</tok> <tok cat="NNS">monolayers</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">led</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">functional</tok> <tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">lymphocytes</tok></cons> <cons cat="VP"><tok cat="VBG">expressing</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Notch1/TAN-1</tok> <tok cat="NN">receptor</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1032962608@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok></cons> <cons cat="VP"><tok cat="VBD">correlated</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">initiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBG">signaling</tok> <tok cat="RB">downstream</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Notch</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">as</tok> <tok cat="VBN">evidenced</tok> <tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">HES-1</tok> <tok cat="NNS">transcripts</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">co-cultivated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD23</tok> <tok cat="NNS">transcripts</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">co-cultivated</tok> <tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1032962609@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" ref="i9" role="SBJ" null="NONE"></cons><cons cat="VP"><cons cat="ADJP" role="PRD"><tok cat="JJ">Consistent</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">Rel/NF-kappaB-dependent</tok> <tok cat="NN">induction</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i9" role="SBJ"><tok cat="NN">Jagged1</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="S"><cons cat="NP" ref="i9" id="i10" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADVP"><tok cat="RB">highly</tok></cons> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">splenic</tok> <tok cat="NN">B</tok> <tok cat="NNS">cells</tok> <cons cat="SBAR"><cons cat="WHADVP" id="i11"><tok cat="WRB">where</tok></cons> <cons cat="S"><cons cat="NP" id="i12" role="SBJ"><tok cat="NN">c-Rel</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">constitutively</tok></cons><cons cat="ADVP" ref="i11" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1032962610@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i13" role="SBJ"><tok cat="NN">c-Rel</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">trigger</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Notch</tok> <tok cat="NN">signaling</tok> <tok cat="NN">pathway</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">neighboring</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i13" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">inducing</tok> <tok cat="NN">jagged1</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">Jagged1</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">B-cell</tok> <tok cat="NN">activation</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">differentiation</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">function</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1032962611@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBP">highlight</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">potential</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">interplay</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Notch</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">immune</tok> <tok cat="NN">system</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1032984501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Transcriptional</tok> <tok cat="NN">control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-5</tok> <tok cat="NN">gene</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">helper</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="NN">IL-5</tok> <tok cat="NN">synthesis</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">regulated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">independently</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-2</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">IL-4</tok> <tok cat="NN">synthesis</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1032984502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">BACKGROUND</tok></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NN">IL-5</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">fundamentally</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">eosinophilic</tok> <tok cat="NN">inflammation</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@10@@oe@16-12-2010 1032984503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-5</tok> <tok cat="NN">production</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">effective</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">management</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">allergic</tok> <tok cat="NNS">diseases</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1032984504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">OBJECTIVE</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" id="i3" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">aimed</tok> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">find</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">regulate</tok> <cons cat="NP"><cons cat="NP" id="i5"><tok cat="DT">the</tok> <tok cat="NN">IL-5</tok> <tok cat="NN">gene</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="ADVP"><tok cat="RB">selectively</tok></cons> <cons cat="VP"><tok cat="VB">control</tok> <cons cat="NP"><tok cat="NN">IL-5</tok> <tok cat="NN">synthesis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1032984505@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="NP"><tok cat="NNS">METHODS</tok></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i6" role="SBJ"><cons cat="NP"><tok cat="JJ">Allergen-specific</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">clones</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NNS">hybridomas</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">established</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">asthma</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-5</tok> <tok cat="NN">gene</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">investigated</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">transient</tok> <tok cat="NN">transfection</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">electrophoretic</tok> <tok cat="NN">mobility</tok> <tok cat="NN">shift</tok> <tok cat="NN">analysis</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@39@@oe@16-12-2010 1032984506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">RESULTS</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="JJ">human</tok> <tok cat="NN">IL-5</tok> <tok cat="NN">promoter/enhancer-luciferase</tok> <tok cat="NN">gene</tok> <tok cat="NN">construct</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">pIL-5(-511)</tok><tok cat="NN">Luc</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">transcribed</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">IL-5-producing</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">clones</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="JJ">IL-5-nonproducing</tok> <tok cat="NNS">clones</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1032984507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i9" role="SBJ"><tok cat="NN">pIL-5(-511)</tok><tok cat="NN">Luc</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">transcribed</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NNS">hybridomas</tok></cons> <cons cat="VP"><tok cat="VBN">derived</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">fusion</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">IL-5-producing</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">clones</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">IL-5</tok> <tok cat="JJ">gene-nonexpressing</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">line</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">hybridomas</tok></cons> <cons cat="VP"><tok cat="VBN">derived</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">IL-5-nonproducing</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">clones</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1032984508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i10" role="SBJ"><tok cat="NN">IL-5</tok> <tok cat="NN">synthesis</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP" syn="COOD"><cons cat="CONJP"><tok cat="RB">not</tok> <tok cat="RB">only</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP" id="i11"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">T-cell</tok> <tok cat="NN">receptor</tok> <tok cat="NN">stimulation</tok></cons></cons></cons> <cons cat="CONJP"><tok cat="CC">but</tok> <tok cat="RB">also</tok></cons> <cons cat="VP"><cons map="i11" cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">IL-2</tok> <tok cat="NN">receptor</tok> <tok cat="NN">stimulation</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1032984509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i12" role="SBJ"><cons cat="NP"><tok cat="NN">Binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NF-AT</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">TcR</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">stimulation</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">although</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="EX">there</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">no</tok> <tok cat="JJ">significant</tok> <tok cat="NN">upregulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">stimulation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1032984510@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">CONCLUSION</tok></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" id="i13" role="SBJ"><cons cat="NP"><tok cat="NN">IL-5</tok> <tok cat="NN">synthesis</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">helper</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">regulated</tok> <cons cat="NP" ref="i13" null="NONE"></cons><cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">level</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1032984511@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i16" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="JJ">unique</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">mechanism</tok></cons> <cons cat="ADJP"><tok cat="JJ">distinct</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP" id="i14"><tok cat="DT">those</tok></cons> <cons cat="VP"><tok cat="VBG">regulating</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-2</tok> <cons cat="NP" ref="i15" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">IL-4</tok> <cons cat="NP" ref="i15" null="RNR"></cons></cons><cons cat="NP" id="i15"><tok cat="NNS">genes</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">seems</tok> <cons cat="S"><cons cat="NP" ref="i16" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">control</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-5</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1032984512@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Selective</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-5</tok> <tok cat="NN">gene</tok> <tok cat="NN">transcription</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">useful</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">treating</tok> <cons cat="NP"><tok cat="JJ">eosinophlic</tok> <tok cat="NN">inflammation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1032995801@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">low</tok> <tok cat="NN">shear</tok> <tok cat="JJ">flow-induced</tok> <tok cat="NNS">HAEC</tok> <tok cat="NN">VCAM-1</tok> <tok cat="NN">expression</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">monocyte</tok> <tok cat="NN">adhesion</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1032995802@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">recently</tok></cons> <cons cat="VP"><tok cat="VBD">reported</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="JJ">prolonged</tok> <tok cat="NN">exposure</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">aortic</tok> <tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">HAEC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">low</tok> <tok cat="NN">shear</tok> <tok cat="NN">stress</tok> <tok cat="NN">flow</tok> <tok cat="NNS">patterns</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">sustained</tok> <tok cat="NN">increase</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">activated</tok> <tok cat="NN">form</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">regulator</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">factor-kappaB</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1032995803@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">investigate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">hypothesis</tok></cons> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">low</tok> <tok cat="JJ">shear-induced</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">responsible</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="VBN">enhanced</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">vascular</tok> <tok cat="NN">cell</tok> <tok cat="NN">adhesion</tok> <tok cat="NN">molecule</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">VCAM-1</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBG">resulting</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">augmented</tok> <tok cat="JJ">endothelial</tok> <tok cat="NN">cell-monocyte</tok> <tok cat="LRB">(</tok><tok cat="NN">EC-Mn</tok><tok cat="RRB">)</tok> <tok cat="NN">adhesion</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">this</tok> <tok cat="NN">activation</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">dependent</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">intracellular</tok> <tok cat="JJ">oxidant</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1032995804@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP" adv="TMP"><tok cat="IN">Before</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">exposure</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">low</tok> <tok cat="NN">shear</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">2</tok> <tok cat="NN">dyn/cm2</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="CD">6</tok> <tok cat="NN">h</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><tok cat="NNS">HAEC</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">preincubated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><cons cat="NP" syn="COOD" id="i3"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">antioxidants</tok> <tok cat="NN">pyrrolidine</tok> <tok cat="NN">dithiocarbamate</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">PDTC</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">N-acetyl-L-cysteine</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NAC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1032995805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PDTC</tok></cons> <cons cat="ADVP"><tok cat="RB">strongly</tok></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">low</tok> <tok cat="JJ">shear-induced</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">VCAM-1</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">EC-Mn</tok> <tok cat="NN">adhesion</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1032995806@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Paradoxically</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">NAC</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">exerted</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">positive</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">low</tok> <tok cat="JJ">shear-induced</tok> <tok cat="NN">VCAM-1</tok> <tok cat="NN">expression</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">EC-Mn</tok> <tok cat="NN">adhesion</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">only</tok> <tok cat="RB">slightly</tok></cons> <tok cat="JJ">downregulated</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1032995807@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" id="i4" role="SBJ"><cons cat="NP"><tok cat="JJ">cytokine-induced</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">VCAM-1</tok> <tok cat="NN">expression</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">blocked</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">PDTC</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">NAC</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1032995808@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">key</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">low</tok> <tok cat="JJ">shear-induced</tok> <tok cat="NN">VCAM-1</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="NNS">pathways</tok></cons> <cons cat="VP"><tok cat="VBG">mediating</tok> <cons cat="NP"><tok cat="JJ">low</tok> <tok cat="NN">shear-</tok> <tok cat="CC">and</tok> <tok cat="JJ">cytokine-induced</tok> <tok cat="NN">EC-Mn</tok> <tok cat="NN">adhesion</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADVP"><tok cat="RB">differentially</tok></cons> <cons cat="VP"><tok cat="VBN">regulated</tok><cons cat="NP" ref="i5" null="NONE"></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1033018901@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">Nuclear</tok> <tok cat="NN">localization</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="ADJP" null="QSTN"></cons><tok cat="NN">formation</tok></cons></cons> <cons cat="PP" id="i1"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">beta-catenin-lymphoid</tok> <tok cat="NN">enhancer</tok> <tok cat="NN">factor</tok> <tok cat="CD">1</tok> <tok cat="NNS">complexes</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <tok cat="RB">not</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">sufficient</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1033018902@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Wnt</tok> <tok cat="NN">signaling</tok> <tok cat="NN">pathway</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">beta-catenin</tok></cons> <cons cat="VP"><tok cat="VBZ">accumulates</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nucleus</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHADVP" id="i2"><tok cat="WRB">where</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="VBZ">cooperates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">LEF/TCF</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">lymphoid</tok> <tok cat="NN">enhancer</tok> <tok cat="NN">factor</tok> <tok cat="CC">and</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">factor</tok></cons></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons><cons cat="ADVP" ref="i2" null="T"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1033018903@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i4"><tok cat="IN">by</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">beta-catenin</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">undergoes</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">shift</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">location</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">participates</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">transcription</tok></cons></cons></cons></cons></cons> <cons cat="PP" ref="i4" null="T"></cons></cons></cons></cons></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="JJ">unknown</tok><cons cat="NP" ref="i3" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1033018904@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="ADVP"><tok cat="RB">here</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NN">beta-catenin</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">imported</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nucleus</tok></cons> <cons cat="ADVP"><tok cat="RB">independently</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">LEF/TCF</tok> <tok cat="NN">binding</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">exported</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NNS">nuclei</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1033018905@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">introduced</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">small</tok> <tok cat="NN">deletion</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">beta-catenin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">Delta19</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i7"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">disrupts</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">LEF-1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">E-cadherin</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">APC</tok></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="NN">axin</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1033018906@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">Delta19</tok> <tok cat="NN">beta-catenin</tok> <tok cat="NN">mutant</tok></cons> <cons cat="VP"><tok cat="VBZ">localizes</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nucleus</tok></cons></cons> <cons cat="SBAR"><tok cat="IN">because</tok> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADVP"><tok cat="RB">efficiently</tok></cons> <cons cat="VP"><tok cat="VBN">sequestered</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cytoplasm</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1033018907@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">localization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Delta19</tok></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">definitively</tok></cons> <cons cat="VP"><tok cat="VBZ">demonstrates</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i9"><tok cat="IN">by</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">beta-catenin</tok></cons> <cons cat="VP"><tok cat="VBZ">localizes</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nucleus</tok></cons></cons> <cons cat="PP" ref="i9" null="T"></cons></cons></cons></cons></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">completely</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">independent</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">LEF/TCF</tok> <tok cat="NNS">factors</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1033018908@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">beta-Catenin</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">LEF-1</tok> <tok cat="NNS">complexes</tok></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><tok cat="NN">reporter</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <cons cat="NP"><tok cat="VBN">transformed</tok> <tok cat="NN">T-lymphocyte</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">Jurkat</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="RB">even</tok> <tok cat="IN">though</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">both</tok> <tok cat="NNS">factors</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">nuclear</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1033018909@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Thus</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">localization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">both</tok> <tok cat="NNS">factors</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nucleus</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">sufficient</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1033018910@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Excess</tok> <tok cat="NN">beta-catenin</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">squelch</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">reporter</tok> <tok cat="NN">gene</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">LEF-1-beta-catenin</tok> <tok cat="NNS">complexes</tok></cons></cons></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="NP"><tok cat="NN">VP16</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1033018911@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" id="i10" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">Taken</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">together</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">a</tok> <tok cat="JJ">third</tok> <tok cat="NN">component</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">necessary</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">this</tok> <tok cat="JJ">third</tok> <tok cat="NN">component</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">vary</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">type</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1033027401@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Paradoxical</tok> <tok cat="JJ">priming</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NN">production</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@9@@oe@16-12-2010 1033027402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-10</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">well-known</tok> <tok cat="JJ">immunosuppressive</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and/or</tok> <cons cat="NP"><cons cat="ADJP" null="QSTN"></cons><tok cat="JJ">anti-inflammatory</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons></cons><cons cat="NP" id="i1"><tok cat="NN">cytokine</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@9@@oe@16-12-2010 1033027403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">report</tok> <cons cat="NP"><cons cat="NP"><cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok> <tok cat="JJ">experimental</tok></cons> <tok cat="NNS">studies</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i2"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-10</tok></cons> <cons cat="VP"><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">primed</tok> <cons cat="NP"><tok cat="NNS">leukocytes</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">led</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="VBN">enhanced</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">TNF</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">further</tok> <tok cat="NN">stimulation</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">lipopolysaccharide</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">LPS</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><cons cat="PP" ref="i2" null="T"></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1033027404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">Monocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">PBMC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">prepared</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">whole</tok> <tok cat="NN">blood</tok></cons> <cons cat="VP"><tok cat="VBN">maintained</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="CD">20</tok> <tok cat="NN">h</tok></cons></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="CD">37</tok> <tok cat="NNS">degrees</tok> <tok cat="NN">C</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">recombinant</tok> <tok cat="JJ">human</tok> <tok cat="NN">IL-10</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="VBN">enhanced</tok> <tok cat="NN">capacity</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">produce</tok> <cons cat="NP"><tok cat="NN">TNF</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">LPS</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1033027405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">TNF</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" id="i5" role="SBJ"><cons cat="NP"><tok cat="JJ">LPS-induced</tok> <tok cat="NN">IL-6</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">spontaneous</tok> <tok cat="NN">IL-1ra</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><cons cat="NP" id="i6"><tok cat="NN">production</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">enhanced</tok><cons cat="NP" ref="i5" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1033027406@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i7"><tok cat="WRB">When</tok></cons> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="VBN">isolated</tok> <tok cat="NN">PBMC</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><cons cat="ADVP"><tok cat="RB">first</tok></cons> <cons cat="VP"><tok cat="VBN">cultured</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="CD">20</tok> <tok cat="NN">h</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">Teflon</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">prevent</tok> <cons cat="NP"><tok cat="NN">adherence</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">washed</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">remove</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">then</tok></cons> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">further</tok></cons> <cons cat="VP"><tok cat="VBN">cultured</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">plastic</tok> <tok cat="NNS">dishes</tok></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">additional</tok> <tok cat="CD">20</tok> <tok cat="NN">h</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">LPS</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">IL-1beta</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i9" role="SBJ"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="VBN">enhanced</tok> <tok cat="NN">release</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TNF</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">observed</tok><cons cat="NP" ref="i9" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@52@@oe@16-12-2010 1033027407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">case</tok></cons> <cons cat="SBAR"><cons cat="WHADVP" id="i10"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" id="i11" role="SBJ"><tok cat="NN">PBMC</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="JJ">pre-cultured</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">plastic</tok> <tok cat="NNS">multidishes</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons></cons></cons><cons cat="ADVP" ref="i10" null="T"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1033027408@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i12" role="SBJ"><tok cat="NN">TNF</tok> <tok cat="NN">mRNA</tok> <tok cat="NN">expression</tok> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">LPS</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">decreased</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="SBAR" adv="TMP"><tok cat="WRB">when</tok> <cons cat="S"><cons cat="NP" id="i14" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">pre-treatment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PBMC</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">performed</tok> <cons cat="NP" ref="i14" null="NONE"></cons><cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">plastic</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">this</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">case</tok></cons> <cons cat="SBAR"><cons cat="WHADVP" id="i15"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" id="i16" role="SBJ"><tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="JJ">pre-cultured</tok> <cons cat="NP" ref="i16" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">Teflon</tok></cons></cons><cons cat="ADVP" ref="i15" null="T"></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1033027409@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP" id="i17"><tok cat="NN">NFkappaB</tok> <tok cat="NN">translocation</tok></cons> <cons cat="VP"><tok cat="VBG">following</tok> <cons cat="NP"><tok cat="NN">LPS</tok> <tok cat="NN">activation</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><cons cat="ADJP"><tok cat="JJR">higher</tok> <cons cat="PP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-10</tok> <tok cat="NN">pre-treatment</tok></cons> <cons cat="PP" id="i20"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">Teflon</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons map="i20" cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">plastic</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1033027410@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP" role="PRD"><tok cat="RB">Interestingly</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i18" role="SBJ"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="VBN">enhanced</tok> <tok cat="NN">frequency</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CD16</tok> <cons cat="NP" ref="i19" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">CD68(+)</tok> <cons cat="NP" ref="i19" null="RNR"></cons></cons><cons cat="NP" id="i19"><tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">among</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">CD14(+)</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i18" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">independently</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">pre-culture</tok> <tok cat="NNS">conditions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">PBMC</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1033027411@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Altogether</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">IL-10-induced</tok> <tok cat="NN">up-regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NN">production</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">depends</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">prevention</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">monocyte</tok> <tok cat="NN">adherence</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">red</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">whole</tok> <tok cat="NN">blood</tok> <tok cat="NNS">assays</tok></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">cultures</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PBMC</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">Teflon</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1033027412@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">adherence</tok> <tok cat="NN">parameter</tok></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">no</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">IL-10-induced</tok> <tok cat="NN">modulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="NN">monocyte</tok> <tok cat="NN">surface</tok> <tok cat="NNS">markers</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1033039601@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">RanBP1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">release</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CRM1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">pore</tok> <tok cat="NN">complex</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">terminal</tok> <tok cat="NN">step</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">export</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1033039602@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">recently</tok></cons> <cons cat="VP"><tok cat="VBD">developed</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">assay</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i1"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">export</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBG">shuttling</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">NFAT</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">factor</tok> <tok cat="IN">of</tok> <tok cat="VBN">activated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">reconstituted</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">permeabilized</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">GTPase</tok></cons> <cons cat="NP"><tok cat="NN">Ran</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">export</tok> <tok cat="NN">receptor</tok></cons> <cons cat="NP"><tok cat="NN">CRM1</tok></cons></cons></cons></cons><cons cat="PP" ref="i1" null="T"></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1033039603@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="ADVP"><tok cat="RB">now</tok></cons> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">assay</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">identify</tok> <cons cat="NP"><tok cat="DT">another</tok> <tok cat="NN">export</tok> <tok cat="NN">factor</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1033039604@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP" adv="TMP"><tok cat="IN">After</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">preincubation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">permeabilized</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">Ran</tok> <tok cat="NN">mutant</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">can</tok><tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">hydrolyze</tok> <cons cat="NP"><tok cat="NN">GTP</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">RanQ69L</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">cytosol</tok></cons> <cons cat="VP"><tok cat="VBZ">supports</tok> <cons cat="NP"><tok cat="NN">NFAT</tok> <tok cat="NN">export</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CRM1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Ran</tok></cons></cons> <cons cat="ADJP"><tok cat="RB">alone</tok></cons></cons> <cons cat="VP"><tok cat="VBP">do</tok> <tok cat="RB">not</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1033039605@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">RanQ69L</tok> <tok cat="NN">preincubation</tok></cons> <tok cat="VBZ">leads</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">accumulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CRM1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cytoplasmic</tok> <tok cat="NN">periphery</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">pore</tok> <tok cat="NN">complex</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NPC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">association</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">p62</tok> <tok cat="NN">complex</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Can/Nup214</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1033039606@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">RanGTP-dependent</tok> <tok cat="NN">association</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CRM1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">nucleoporins</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">reconstituted</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1033039607@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">By</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">biochemical</tok> <tok cat="NN">fractionation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">reconstitution</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">RanBP1</tok></cons> <cons cat="VP"><tok cat="VBZ">restores</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">export</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">RanQ69L</tok> <tok cat="NN">preincubation</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1033039608@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">It</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBZ">stimulates</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">export</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">cells</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" id="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">have</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">preincubated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">RanQ69L</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1033039609@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">RanBP1</tok> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <tok cat="JJ">Ran-binding</tok> <tok cat="NNS">domains</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">cytoplasmic</tok> <tok cat="NN">nucleoporin</tok></cons> <cons cat="NP"><tok cat="NN">RanBP2</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">promote</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">release</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CRM1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NPC</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1033039610@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" id="i8" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">Taken</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">together</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRPP">our</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">RanGTP</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">important</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">targeting</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">export</tok> <tok cat="NNS">complexes</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cytoplasmic</tok> <tok cat="NN">side</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NPC</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i9" role="SBJ"><cons cat="NP"><tok cat="NN">RanBP1</tok></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">probably</tok></cons> <cons cat="NP"><tok cat="NN">RanBP2</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">dissociation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">export</tok> <tok cat="NNS">complexes</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NPC</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">terminal</tok> <tok cat="NN">step</tok> <tok cat="IN">of</tok> <tok cat="NN">transport</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@48@@oe@16-12-2010 1033156401@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Th1</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Th2</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NN">type</tok> <tok cat="NNS">cytokines</tok></cons></cons></cons> <cons cat="PP"><tok cat="VBG">responding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">HBsAg</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">HBxAg</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">B</tok> <tok cat="NNS">patients</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1033156402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">cytokine</tok> <tok cat="NN">pattern</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NN">antigen</tok> <tok cat="NN">recognition</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">believed</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">exert</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">profound</tok> <tok cat="NN">influence</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">resolution</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NNS">infections</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NN">clearance</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1033156403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">study</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">initiated</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">investigate</tok> <cons cat="SBAR"><tok cat="IN">whether</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">cytokine</tok> <tok cat="NN">imbalance</tok></cons> <cons cat="VP"><tok cat="VBN">oriented</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">toward</tok> <cons cat="NP"><tok cat="NN">Th2</tok> <tok cat="NN">type</tok> <tok cat="NN">response</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">B</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1033156404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="NN">Cytokine</tok> <tok cat="NNS">profiles</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">B</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">analysed</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">RT-PCR</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1033156405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Upon</tok> <cons cat="NP"><tok cat="NN">HBsAg</tok> <tok cat="NN">stimulation</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IFN-gamma</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-2</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-4</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">41</tok><tok cat="NN">%</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="CD">8</tok><tok cat="NN">%</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="CD">41</tok><tok cat="NN">%</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="CD">50</tok><tok cat="NN">%</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">patients</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">respectively</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1033156406@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Among</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">cytokines</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IFN-gamma</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">high</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">serum</tok> <tok cat="NN">AST/ALT</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1033156407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="MD">could</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">prove</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Th2</tok> <tok cat="NN">type</tok> <tok cat="NNS">cytokines</tok></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">protective</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NNS">hepatocytes</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1033156408@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Upon</tok> <cons cat="NP"><tok cat="NN">HBxAg</tok> <tok cat="NN">stimulation</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="EX">there</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">no</tok> <tok cat="JJ">recognizable</tok> <tok cat="NN">association</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NNS">patterns</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">AST/ALT</tok> <tok cat="NNS">levels</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1033156409@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">conclusion</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">Th1</tok> <tok cat="NN">cytokine</tok><tok cat="COMMA">,</tok> <tok cat="NN">IFN-gamma</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">HBsAg-reactive</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">hepatocyte</tok> <tok cat="NN">damage</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">B</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><tok cat="DT">no</tok> <tok cat="NN">counteracting</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Th2</tok> <tok cat="NNS">cytokines</tok></cons> <cons cat="VP"><tok cat="VBN">produced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">those</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">observed</tok><cons cat="NP" ref="i8" null="NONE"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1033198901@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Different</tok> <tok cat="NN">sequence</tok> <tok cat="NNS">requirements</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">erythroid</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">megakaryocytic</tok></cons></cons> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">element</tok> <cons cat="ADJP"><tok cat="JJ">upstream</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">GATA-1</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1033198902@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="JJ">lineage-restricted</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">erythroid</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">megakaryocytic</tok></cons></cons> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1033198903@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">localized</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="CD">317</tok> <tok cat="NN">base</tok> <tok cat="NN">pair</tok> <tok cat="JJ">cis-acting</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">element</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">HS</tok> <tok cat="CD">I</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">hematopoietic-specific</tok> <tok cat="NN">DNase</tok> <tok cat="CD">I</tok> <tok cat="JJ">hypersensitive</tok> <tok cat="NN">site</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">lies</tok> <cons cat="ADVP"><cons cat="NP"><cons cat="QP"><tok cat="RB">approx.</tok> <tok cat="CD">3.7</tok></cons> <tok cat="NNS">kilobases</tok></cons> <tok cat="RB">upstream</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">murine</tok> <tok cat="JJ">hematopoietic-specific</tok> <tok cat="NN">GATA-1</tok> <tok cat="NN">IE</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1033198904@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">HS</tok> <tok cat="CD">I</tok></cons> <cons cat="VP"><tok cat="VBZ">directs</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">high-level</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">reporter</tok> <tok cat="NN">GATA-1/lacZ</tok> <tok cat="NNS">genes</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">primitive</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">definitive</tok></cons></cons> <tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">megakaryocytes</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">transgenic</tok> <tok cat="NNS">mice</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1033198905@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Comparative</tok> <tok cat="NN">sequence</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HS</tok> <tok cat="CD">I</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">human</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">mouse</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">shows</tok> <cons cat="NP"><cons cat="NP"><cons cat="QP"><tok cat="RB">approx.</tok> <tok cat="CD">63</tok></cons><tok cat="NN">%</tok> <tok cat="NN">nucleotide</tok> <tok cat="NN">identity</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <cons cat="ADJP"><tok cat="RBR">more</tok> <tok cat="VBN">conserved</tok></cons> <tok cat="NN">core</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="CD">169</tok> <tok cat="NN">base</tok> <tok cat="NNS">pairs</tok></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">86</tok><tok cat="NN">%</tok> <tok cat="NN">identity</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1033198906@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">core</tok></cons> <cons cat="VP"><tok cat="VBZ">contains</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">GATA</tok> <tok cat="NN">site</tok></cons> <cons cat="VP"><tok cat="VBN">separated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="CD">10</tok> <tok cat="NN">base</tok> <tok cat="NNS">pairs</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">E-box</tok> <tok cat="NN">motif</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1033198907@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="JJ">composite</tok> <tok cat="NN">motif</tok></cons> <cons cat="VP"><tok cat="VBZ">binds</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">multi-protein</tok> <tok cat="JJ">hematopoietic-specific</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">complex</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">includes</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">GATA-1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">SCL/tal-1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">E2A</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">Lmo2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Ldb-1</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1033198908@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Point</tok> <tok cat="NNS">mutations</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">GATA</tok> <tok cat="NN">site</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">abolishes</tok> <cons cat="NP"><tok cat="NNS">HS</tok> <tok cat="CD">I</tok> <tok cat="NN">function</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">mutation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">E-box</tok> <tok cat="NN">motif</tok></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">still</tok></cons> <cons cat="VP"><tok cat="VBZ">allows</tok> <cons cat="NP"><tok cat="NN">reporter</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">both</tok> <tok cat="NNS">lineages</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1033198909@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Strict</tok> <tok cat="NN">dependence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HS</tok> <tok cat="CD">I</tok> <tok cat="NN">activity</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">GATA</tok> <tok cat="NN">site</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">implies</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">assembly</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" id="i4"><tok cat="DT">a</tok> <tok cat="NN">protein</tok> <tok cat="NN">complex</tok></cons> <cons cat="VP"><tok cat="VBG">containing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">GATA-factor</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="ADVP"><tok cat="RB">presumably</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">GATA-1</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">GATA-2</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">critical</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBG">activating</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="VP"><tok cat="VBG">maintaining</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><cons cat="NP" id="i5"><tok cat="PRPP">its</tok> <tok cat="NN">function</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1033198910@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="RB">Further</tok> <tok cat="NN">dissection</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="CD">317</tok> <tok cat="NN">base</tok> <tok cat="NN">pair</tok> <tok cat="NN">region</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">demonstrates</tok> <cons cat="SBAR"><tok cat="IN">that</tok><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="SBAR"><tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="DT">all</tok> <tok cat="CD">317</tok> <tok cat="NN">base</tok> <tok cat="NNS">pairs</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">megakaryocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7" role="SBJ"><cons cat="ADVP"><tok cat="RB">only</tok></cons> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">5'</tok> <tok cat="CD">62</tok> <tok cat="NN">base</tok> <tok cat="NNS">pairs</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">needed</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">erythroid-specific</tok> <tok cat="NN">reporter</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1033198911@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">differential</tok> <tok cat="NN">lineage</tok> <tok cat="NNS">requirements</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">HS</tok> <tok cat="CD">I</tok> <tok cat="NN">element</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1033947501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Monocyte</tok> <tok cat="NN">arrest</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">transmigration</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">inflamed</tok> <tok cat="NN">endothelium</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">shear</tok> <tok cat="NN">flow</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">adenovirus-mediated</tok> <tok cat="NN">gene</tok> <tok cat="NN">transfer</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IkappaB-alpha</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1033947502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Mobilization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">factor-kappaB</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">activates</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">genes</tok></cons> <cons cat="VP"><tok cat="VBG">encoding</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NN">adhesion</tok> <tok cat="NNS">molecules</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">chemokines</tok></cons></cons></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">contribute</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">monocyte</tok> <tok cat="NN">infiltration</tok></cons> <cons cat="ADJP"><tok cat="JJ">critical</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">atherogenesis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1033947503@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="NN">Inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">achieved</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">pharmacological</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">genetic</tok></cons></cons> <tok cat="NNS">approaches</tok></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="NN">monocyte</tok> <tok cat="NNS">interactions</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="VBN">activated</tok> <tok cat="NN">endothelium</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">shear</tok> <tok cat="NN">flow</tok></cons> <cons cat="PP" adv="TMP"><tok cat="VBG">following</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">transfer</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="NP"><tok cat="NN">IkappaB-alpha</tok></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">studied</tok><cons cat="NP" ref="i6" null="NONE"></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1033947504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">overexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IkappaB-alpha</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">recombinant</tok> <tok cat="NN">adenovirus</tok></cons></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">prevented</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor-alpha</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="JJ">-induced</tok> <tok cat="NN">degradation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IkappaB-alpha</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">suppressed</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">upregulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">vascular</tok> <tok cat="NN">cell</tok> <tok cat="NN">adhesion</tok> <tok cat="NN">molecule-1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">VCAM-1</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">intercellular</tok> <tok cat="NN">adhesion</tok> <tok cat="NN">molecule-1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">ICAM-1</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">E-selectin</tok> <tok cat="NN">mRNA</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">surface</tok> <tok cat="NN">protein</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">upregulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">transcripts</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NNS">chemokines</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="NN">monocyte</tok> <tok cat="NN">chemoattractant</tok> <tok cat="NN">protein</tok> <tok cat="CD">1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MCP-1</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">growth-related</tok> <tok cat="NN">activity-alpha</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">GRO-alpha</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@75@@oe@16-12-2010 1033947505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="DT">This</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">reduction</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NN">MCP-1</tok> <tok cat="NN">secretion</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">GRO-alpha</tok> <tok cat="NN">immobilization</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1033947506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Adhesion</tok> <tok cat="NNS">assays</tok></cons> <cons cat="PP"><tok cat="IN">under</tok> <cons cat="NP"><tok cat="JJ">physiological</tok> <tok cat="NN">shear</tok> <tok cat="NN">flow</tok> <tok cat="NNS">conditions</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i9" role="SBJ"><cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">firm</tok> <tok cat="NN">arrest</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">spreading</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">transmigration</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="PP"><tok cat="JJ">TNF-alpha-activated</tok> <tok cat="NN">endothelium</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">markedly</tok></cons> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">IkappaB-alpha</tok> <tok cat="NN">overexpression</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1033947507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Inhibition</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">monoclonal</tok> <tok cat="NNS">antibodies</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">peptide</tok> <tok cat="NNS">antagonists</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">inferred</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">this</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="PP"><tok cat="JJ">due</tok> <tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">reduced</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Ig</tok> <tok cat="NN">integrin</tok> <tok cat="NN">ligand</tok></cons></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">chemokines</tok></cons> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">specifically</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">events</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1033947508@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i11" role="SBJ"><cons cat="NP"><tok cat="NN">rolling</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">increased</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">IkappaB-alpha</tok> <tok cat="NN">transfer</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">partly</tok></cons> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">P-selectin</tok></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i12" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="VBD">appeared</tok> <cons cat="S"><cons cat="NP" ref="i12" id="i13" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="JJ">unaffected</tok> <cons cat="NP" ref="i13" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">E-selectin</tok> <tok cat="NN">induction</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1033947509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Thus</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRPP">our</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">provide</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">novel</tok> <tok cat="NN">evidence</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">selective</tok> <tok cat="NN">modulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">adenoviral</tok> <tok cat="NN">transfer</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IkappaB-alpha</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">impairs</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">multiple</tok> <tok cat="JJ">endothelial</tok> <tok cat="NN">gene</tok> <tok cat="NNS">products</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">subsequent</tok> <tok cat="NN">monocyte</tok> <tok cat="NN">arrest</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">emigration</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">shear</tok> <tok cat="NN">flow</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">thus</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">monocyte</tok> <tok cat="NN">infiltration</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">atherosclerotic</tok> <tok cat="NNS">plaques</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1033948201@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" id="i1" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Protein</tok> <tok cat="NN">kinase</tok> <tok cat="NN">B</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">c-Akt</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">phosphatidylinositol</tok> <tok cat="NN">3-kinase</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><cons cat="NP"><tok cat="NN">erythropoietin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">EPO</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">HCD57</tok> <tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">constitutively</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">active</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">EPO-independent</tok><tok cat="COMMA">,</tok> <tok cat="JJ">apoptosis-resistant</tok> <tok cat="NN">subclone</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">HCD57-SREI</tok> <tok cat="NNS">cells</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1033948202@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">erythropoietin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">EPO</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBP">stem</tok> <tok cat="NN">cell</tok> <tok cat="NN">factor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">SCF</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">activated</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">protein</tok> <tok cat="NN">kinase</tok> <tok cat="NN">B</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">PKB/Akt</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">EPO-dependent</tok> <tok cat="NN">HCD57</tok> <tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1033948203@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="ADVP"><tok cat="RBR">better</tok></cons> <cons cat="VP"><tok cat="VB">understand</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">signals</tok> <tok cat="VBG">controlling</tok> <tok cat="NN">proliferation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">viability</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">resist</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">EPO</tok></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><cons cat="VP"><tok cat="VBN">subcloned</tok> <cons cat="NP" ref="i3" null="NONE"></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBN">characterized</tok> <cons cat="NP" ref="i3" null="NONE"></cons></cons><cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">HCD57-SREI</tok> <tok cat="NNS">cells</tok></cons><tok cat="RRB">)</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1033948204@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="JJ">Constitutive</tok> <tok cat="NNS">activations</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">PKB/Akt</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">STAT5a</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5b</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">noted</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="JJ">EPO-independent</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1033948205@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PI3-kinase</tok> <tok cat="NN">activity</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">upstream</tok> <tok cat="NN">activator</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PKB/Akt</tok></cons></cons></cons> <cons cat="SBAR"><tok cat="IN">because</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">PI3-kinase</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="NP"><tok cat="NN">LY294002</tok></cons></cons> <cons cat="VP"><tok cat="VBD">blocked</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="JJ">constitutive</tok> <tok cat="NN">PKB/Akt</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">factor-dependent</tok> <tok cat="NN">PKB/Akt</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1033948206@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">LY294002</tok> <tok cat="NN">study</tok></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">proliferation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">viability</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">HCD57-SREI</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">HCD57</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">correlated</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PKB/Akt</tok></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">PKB/Akt</tok> <tok cat="NN">activity</tok></cons> <cons cat="ADJP"><tok cat="RB">alone</tok></cons></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">protect</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1033948207@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Treatment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HCD57</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">SCF</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBD">activated</tok> <cons cat="NP"><tok cat="NN">PKB/Akt</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">protect</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1033948208@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">result</tok></cons> <cons cat="VP"><tok cat="VBD">suggested</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PKB/PI3-kinase</tok> <tok cat="NN">activity</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" syn="COOD" role="PRD"><cons cat="ADJP"><tok cat="JJ">necessary</tok></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="ADJP"><tok cat="JJ">sufficient</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">promote</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">viability</tok></cons> <tok cat="CC">and/or</tok> <cons cat="NP"><tok cat="NN">proliferation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1033948209@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Constitutive</tok> <tok cat="NN">STAT5</tok> <tok cat="NN">activity</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP" id="i6"><tok cat="DT">an</tok> <tok cat="JJ">unknown</tok> <tok cat="NN">pathway</tok></cons> <cons cat="VP"><tok cat="RB">not</tok> <tok cat="VBG">including</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">JAK2</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">EPOR</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">act</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">concert</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">constitutive</tok> <tok cat="NN">PI3-kinase/PKB/Akt</tok> <tok cat="NN">pathway</tok></cons></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">protect</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">EPO-independent</tok> <tok cat="NN">HCD57-SREI</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VB">promote</tok> <cons cat="NP"><tok cat="JJ">limited</tok> <tok cat="NN">proliferation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1034717501@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">SLP-76</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Vav</tok></cons></cons> <cons cat="VP"><tok cat="NN">function</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">separate</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">overlapping</tok> <cons cat="NP"><tok cat="NNS">pathways</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">augment</tok> <cons cat="NP"><tok cat="NN">interleukin-2</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1034717502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">SLP-76</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Vav</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="CD">two</tok> <tok cat="JJ">hematopoietic</tok> <tok cat="NN">cell</tok> <tok cat="JJ">specific</tok> <tok cat="NNS">molecules</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">critical</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">development</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">activation</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1034717503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP" adv="TMP"><tok cat="VBG">Following</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">antigen</tok> <tok cat="NN">receptor</tok> <tok cat="NN">stimulation</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">SLP-76</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Vav</tok></cons></cons> <cons cat="ADVP"><tok cat="DT">both</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">undergo</tok> <cons cat="NP"><tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">associate</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">each</tok> <tok cat="JJ">other</tok></cons></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">SH2</tok> <tok cat="NN">domain</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Vav</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">phosphorylated</tok> <tok cat="NNS">tyrosines</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">SLP-76</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1034717504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">SLP-76</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Vav</tok></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">synergistic</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="CD">-2</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activity</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1034717505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">report</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="CD">two</tok> <tok cat="NNS">tyrosines</tok></cons><cons cat="PRN"><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Tyr-113</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Tyr-128</tok></cons></cons><tok cat="COMMA">,</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">SLP-76</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">Vav</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="UCP" syn="COOD"><tok cat="CC">both</tok> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">intact</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1034717506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Surprisingly</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">find</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">SLP-76</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Vav</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">cooperation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">augmenting</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">as</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="DT">the</tok> <tok cat="CD">two</tok> <tok cat="NNS">molecules</tok></cons> <cons cat="VP"><tok cat="VBP">appear</tok> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">function</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">different</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="ADJP"><tok cat="JJ">upstream</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1034717507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Overexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">SLP-76</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Jurkat</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">potentiates</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">activities</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">factor</tok> <tok cat="IN">of</tok> <tok cat="VBN">activated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1034717508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">overexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Vav</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">leads</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="VBN">enhanced</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">factor</tok> <tok cat="IN">of</tok> <tok cat="VBN">activated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok> <tok cat="NN">activity</tok></cons></cons> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">affecting</tok> <cons cat="NP"><tok cat="NN">AP-1</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1034717509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Additionally</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">overexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Vav</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="NN">SLP-76</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">augments</tok> <cons cat="NP"><tok cat="JJ">CD28-induced</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activity</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1034717510@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="VP"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">synergy</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">SLP-76</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Vav</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">regulating</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">reflects</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cooperation</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP"><tok cat="JJ">different</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">pathways</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1034834001@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Human</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">leukemia</tok> <tok cat="NN">virus</tok> <tok cat="NN">type</tok> <tok cat="CD">1</tok> <tok cat="NN">Tax</tok> <tok cat="NN">protein</tok></cons> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT1</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NNS">genes</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">T-cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1034834002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Human</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">leukemia</tok> <tok cat="NN">virus</tok> <tok cat="NN">type</tok> <tok cat="CD">1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">HTLV-1</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">Tax</tok></cons> <cons cat="VP"><tok cat="VBZ">transforms</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NNS">T-cells</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="CD">-2</tok></cons> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1034834003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">STAT</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">family</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">play</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">pivotal</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cytokine-induced</tok> <tok cat="NNS">functions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">various</tok> <tok cat="NN">type</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1034834004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">investigated</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">involvement</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">STATs</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transformation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">T-cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">HTLV-1</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1034834005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">HTLV-1-transformed</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">lines</tok></cons> <cons cat="VP"><tok cat="VBD">expressed</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJR">higher</tok> <tok cat="NNS">amounts</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT1</tok><cons cat="NP" ref="i3" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">STAT3</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons></cons><cons cat="NP" id="i3"><tok cat="NN">RNA</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">proteins</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><tok cat="JJ">virus-negative</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1034834006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">human</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">line</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">Tax</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1034834007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-2</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT3</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">HTLV-1-transformed</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">then</tok></cons> <cons cat="VP"><tok cat="VBD">stimulated</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">proliferation</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1034834008@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">IL-2</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <cons cat="NP"><tok cat="DT">neither</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP" id="i5"><tok cat="DT">a</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok></cons> <cons cat="VP"><tok cat="VBG">lacking</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT3</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1034834009@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT1</tok><cons cat="NP" ref="i7" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">STAT3</tok> <cons cat="NP" ref="i7" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok> <cons cat="NP" ref="i7" null="RNR"></cons></cons><cons cat="NP" id="i7"><tok cat="NNS">mRNAs</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">mitogen</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">human</tok> <tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1034834010@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">Tax</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">enhances</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cytokine-induced</tok> <tok cat="NNS">functions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">virus-infected</tok> <tok cat="NNS">T-cells</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">hence</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">play</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">IL-2-dependent</tok> <tok cat="NN">transformation</tok> <tok cat="NNS">steps</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">T-cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">HTLV-1</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1034951301@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="VBN">Targeted</tok> <tok cat="NN">remodeling</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">beta-globin</tok> <tok cat="NN">promoter</tok> <tok cat="NN">chromatin</tok> <tok cat="NN">structure</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">produces</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">expression</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="VBN">decreased</tok> <tok cat="NN">silencing</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1034951302@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">chromatin</tok> <tok cat="NN">structure</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">human</tok> <tok cat="NN">beta-globin</tok> <tok cat="NN">gene</tok> <tok cat="NN">locus</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">assumes</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">transcriptionally-active</tok> <tok cat="NN">conformation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1034951303@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="CD">One</tok> <tok cat="NN">feature</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">chromatin</tok> <tok cat="NN">reorganization</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">formation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">DNase</tok> <tok cat="CD">1</tok> <tok cat="JJ">hypersensitive</tok> <tok cat="NNS">sites</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">regions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">active</tok> <tok cat="NN">globin</tok> <tok cat="NN">gene</tok> <tok cat="NNS">promoters</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1034951304@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">reorganization</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">requires</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">globin</tok> <tok cat="NN">locus</tok> <tok cat="NN">control</tok> <tok cat="NN">region</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">beta-like</tok> <tok cat="NN">globin</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1034951305@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">determine</tok> <cons cat="SBAR"><tok cat="IN">whether</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="PRP">it</tok></cons> <cons cat="S" ref="i6" null="EXP"></cons></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">possible</tok></cons> <cons cat="S" id="i6"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="ADVP"><tok cat="RB">artificially</tok></cons> <cons cat="VP"><tok cat="VB">enhance</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">opening</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">chromatin</tok> <tok cat="NN">structure</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">minimal</tok> <tok cat="NN">beta-globin</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">placed</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">101bp</tok><tok cat="COMMA">,</tok> <tok cat="JJ">erythroid-specific</tok> <tok cat="NN">DNase</tok> <tok cat="CD">1</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">hypersensitive</tok> <tok cat="JJ">site-forming</tok> <tok cat="NN">element</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">HSFE</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">immediately</tok></cons> <cons cat="ADVP"><tok cat="JJ">upstream</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">beta-globin</tok> <tok cat="NN">promoter</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">gene</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1034951306@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">element</tok></cons> <cons cat="VP"><tok cat="VBZ">includes</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBG">binding</tok> <tok cat="NNS">sites</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NF-E2</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">AP-1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Sp-1</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1034951307@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NNS">Constructs</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">stably</tok></cons> <cons cat="VP"><tok cat="VBN">transfected</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="JJ">murine</tok> <tok cat="NN">erythroleukemia</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">promoter</tok> <tok cat="NN">chromatin</tok> <tok cat="NN">structure</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">analyzed</tok><cons cat="NP" ref="i3" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1034951308@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">HSFE</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">area</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">enhanced</tok> <tok cat="NN">DNase</tok> <tok cat="CD">1</tok> <tok cat="NN">hypersensitivity</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBG">extending</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">start</tok> <tok cat="NN">site</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">-300bp</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">artificial</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBD">increased</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">proportion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">beta-globin</tok> <tok cat="NNS">promoters</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">open</tok> <tok cat="NN">chromatin</tok> <tok cat="NN">configuration</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1034951309@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">This</tok> <tok cat="NN">remodeling</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">promoter</tok> <tok cat="NN">chromatin</tok> <tok cat="NN">structure</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">resulted</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="QP"><tok cat="JJ">3-fold</tok></cons> <tok cat="NNS">increases</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">beta-globin</tok> <tok cat="NN">gene</tok> <tok cat="NN">transcription</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">induction</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><tok cat="JJ">long-term</tok> <tok cat="NN">beta-globin</tok> <tok cat="NN">gene</tok> <tok cat="NN">silencing</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1034951310@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="DT">a</tok> <cons cat="ADJP"><tok cat="RB">relatively</tok> <tok cat="JJ">small</tok></cons> <tok cat="JJ">cis-acting</tok> <tok cat="NN">element</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">able</tok> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">enhance</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">remodeling</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">promoter</tok> <tok cat="NN">chromatin</tok> <tok cat="NN">structure</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">resulting</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">beta-globin</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1035224701@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Selection</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">long-term</tok> <tok cat="NN">persistence</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">reactive</tok> <tok cat="NN">CTL</tok> <tok cat="NNS">clones</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">EBV</tok> <tok cat="JJ">chronic</tok> <tok cat="NN">response</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">determined</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">avidity</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD8</tok> <tok cat="JJ">variable</tok> <tok cat="NN">contribution</tok></cons> <cons cat="VP"><tok cat="VBG">compensating</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">differences</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">TCR</tok> <tok cat="NNS">affinities</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1035224702@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Recent</tok> <tok cat="NNS">studies</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">suggested</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">diversity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TCR</tok> <tok cat="NN">repertoire</tok></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><tok cat="JJ">primary</tok> <tok cat="NN">immunization</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">conserved</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">memory</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">progressive</tok> <tok cat="NN">narrowing</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">repertoire</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">take</tok> <tok cat="NN">place</tok> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="NN">recall</tok> <tok cat="NNS">infections</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1035224703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="PRP">It</tok></cons> <cons cat="S" ref="i2" null="EXP"></cons></cons><cons cat="ADVP"><tok cat="RB">now</tok></cons> <cons cat="VP"><tok cat="VBZ">remains</tok> <cons cat="S" id="i2"><cons cat="NP" id="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">investigated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">which</tok> <tok cat="NNS">parameters</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="T"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">determine</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">repertoire</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">memory</tok> <tok cat="NN">response</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">possibly</tok></cons> <cons cat="VP"><tok cat="VB">restrict</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">diversity</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><tok cat="JJ">subsequent</tok> <tok cat="JJ">antigenic</tok> <tok cat="NNS">challenges</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1035224704@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" ref="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">address</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">question</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">took</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">advantage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">panel</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">CD8+</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NNS">clones</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">joint</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">rheumatoid</tok> <tok cat="NN">arthritis</tok> <tok cat="NN">patient</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">selected</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">reactivity</tok></cons> <cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">single</tok> <tok cat="NN">MHC/peptide</tok> <tok cat="NN">complex</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1035224705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Characterization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">both</tok> <tok cat="NN">TCR</tok> <tok cat="NNS">chains</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">documented</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">great</tok> <tok cat="NN">diversity</tok></cons> <cons cat="PP"><tok cat="IN">among</tok> <cons cat="NP"><tok cat="DT">those</tok> <tok cat="NNS">clones</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">persistence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">clonotypes</tok></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">over</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">2-yr</tok> <tok cat="NN">period</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1035224706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Strikingly</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">despite</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">observed</tok> <tok cat="NN">repertoire</tok> <tok cat="NN">heterogeneity</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">all</tok> <tok cat="NNS">clones</tok></cons> <cons cat="VP"><tok cat="VBD">displayed</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">narrow</tok> <tok cat="NN">range</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">MHC/peptide</tok> <tok cat="NN">density</tok> <tok cat="NNS">requirements</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cytotoxicity</tok> <tok cat="NNS">assays</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="NN">ED50</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">9</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="CD">36</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><cons cat="NP" id="i8"><tok cat="NN">nM</tok></cons></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1035224707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i9" role="SBJ"><tok cat="NN">TCR</tok> <tok cat="NNS">affinities</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">then</tok></cons> <cons cat="ADVP"><tok cat="RB">indirectly</tok></cons> <cons cat="VP"><tok cat="VBN">estimated</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">blocking</tok> <cons cat="NP"><tok cat="NN">CD8</tok> <tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">anti-CD8</tok> <tok cat="NN">mAb</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1035224708@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">wide</tok> <tok cat="NN">range</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TCR</tok> <tok cat="NNS">affinities</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">among</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">different</tok> <tok cat="NNS">clonotypes</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i10"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i10" id="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">segregated</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Vbeta</tok> <tok cat="NN">usage</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1035224709@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">thus</tok></cons> <cons cat="VP"><tok cat="VBP">propose</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="DT">an</tok> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vivo</tok> <tok cat="JJ">chronic</tok></cons> <tok cat="NN">response</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">narrow</tok> <tok cat="NN">range</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">avidity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">TCR-CD8</tok> <tok cat="NN">complex</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">conditions</tok> <cons cat="NP"><tok cat="JJ">long-term</tok> <tok cat="NN">clonotype</tok> <tok cat="NN">persistence</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i12" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">level</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CD8</tok> <tok cat="NN">contribution</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">adjusted</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">keep</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">clonotypes</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">variable</tok> <tok cat="NN">TCR</tok> <tok cat="NNS">affinities</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">avidity</tok> <tok cat="NN">window</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@46@@oe@16-12-2010 1035225801@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="ADJP"><tok cat="FW">In</tok> <tok cat="FW">vivo</tok></cons> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">T-lineage</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">leads</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dramatic</tok> <tok cat="NN">decrease</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">proliferation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NN">production</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">cell</tok> <tok cat="NN">apoptosis</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">mitogenic</tok> <tok cat="NNS">stimuli</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">abnormal</tok> <tok cat="NN">thymopoiesis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1035225802@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">understand</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NNS">complexes</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">development</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">generated</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">transgenic</tok> <tok cat="NNS">mice</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i1"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" syn="COOD" id="i2" role="SBJ"><cons cat="NP"><tok cat="NN">RelA</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">c-Rel</tok> <tok cat="NNS">complexes</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">selectively</tok></cons> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">T-lineage</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">specific</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">trans-dominant</tok> <tok cat="NN">form</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">I</tok> <tok cat="NN">kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">alpha</tok></cons></cons></cons></cons></cons></cons><cons cat="PP" ref="i1" null="T"></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@46@@oe@16-12-2010 1035225803@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Transgene</tok> <tok cat="NN">expression</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">thymic</tok> <tok cat="NN">development</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBD">led</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">lowered</tok> <tok cat="NNS">numbers</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">splenic</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dramatic</tok> <tok cat="NN">decrease</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="FW">ex</tok> <tok cat="FW">vivo</tok> <tok cat="JJ">proliferative</tok> <tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">splenic</tok> <tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1035225804@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-2</tok> <cons cat="NP" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-2R</tok> <tok cat="NN">alpha</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">perturbation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">proliferation</tok> <tok cat="NN">response</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">attributable</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">abnormal</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1035225805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-4</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IFN-gamma</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">strongly</tok></cons> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transgenic</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1035225806@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">proliferative</tok> <tok cat="NN">deficiency</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transgenic</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="VBN">increased</tok> <tok cat="NN">apoptosis</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1035225807@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">point</tok> <tok cat="RP">out</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">involvement</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B/Rel</tok> <tok cat="NN">family</tok> <tok cat="NNS">proteins</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">growth</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">pathways</tok></cons></cons></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="CC">either</tok> <cons cat="NP"><tok cat="VBG">regulating</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">signaling</tok></cons></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">functionally</tok></cons> <cons cat="VP"><tok cat="VBG">interfering</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cell</tok> <tok cat="NN">cycle</tok> <tok cat="NN">progression</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1035227301@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">Modulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CD28</tok> <tok cat="NN">expression</tok></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">distinct</tok> <tok cat="JJ">regulatory</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">activation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">replicative</tok> <tok cat="NN">senescence</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1035227302@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="JJ">costimulatory</tok> <tok cat="NN">molecule</tok></cons> <cons cat="NP"><tok cat="NN">CD28</tok></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">restricted</tok> <tok cat="NN">tissue</tok> <tok cat="NN">distribution</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="NN">plasmacytoma</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1035227303@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">Although</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NN">CD28</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">constitutively</tok></cons> <cons cat="VP"><tok cat="VBN">expressed</tok><cons cat="NP" ref="i2" null="NONE"></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i3" role="SBJ"><tok cat="PRPP">its</tok> <tok cat="NN">expression</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">transiently</tok></cons> <cons cat="VP"><tok cat="VBN">down-regulated</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="VBG">following</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">declines</tok> <cons cat="ADVP"><tok cat="RB">progressively</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons> <tok cat="NN">senescence</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1035227304@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="FW">In</tok> <tok cat="FW">vivo</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" id="i4" role="SBJ"><cons cat="NP"><tok cat="JJ">CD8+</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <tok cat="CC">and</tok><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RBR">less</tok> <tok cat="RB">frequently</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">CD4+</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="ADVP"><tok cat="RB">completely</tok></cons> <cons cat="VP"><tok cat="VB">lose</tok> <cons cat="NP"><tok cat="NN">CD28</tok> <tok cat="NN">surface</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NNS">infections</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">aging</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1035227305@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok></cons> <cons cat="VP"><tok cat="VBZ">correlates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">changes</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="JJ">protein-binding</tok> <tok cat="NNS">activities</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="CD">two</tok> <tok cat="NNS">motifs</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">site</tok> <tok cat="NN">alpha</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">beta</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">CD28</tok> <tok cat="JJ">minimal</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1035227306@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" id="i5" role="SBJ"><tok cat="CC">Both</tok> <cons cat="NP"><tok cat="NN">alpha-</tok> <cons cat="NP" null="QSTN"></cons><cons cat="NP" ref="i6" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">beta-bound</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><cons cat="NP" id="i6"><tok cat="NNS">complexes</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><cons cat="ADVP"><tok cat="RB">only</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">lymphoid</tok> <tok cat="NNS">tissues</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">CD28+</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="VBN">transformed</tok> <tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1035227307@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">complexes</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">coordinately</tok></cons> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">except</tok> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">replicative</tok> <tok cat="NN">senescence</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i8"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">characterized</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">down-modulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">site</tok> <tok cat="NN">beta-</tok> <cons cat="NP" ref="i14" null="QSTN"></cons></cons><tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP" id="i14"><tok cat="NN">site</tok> <tok cat="JJ">alpha-binding</tok> <tok cat="NNS">activities</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1035227308@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok></cons> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">parallel</tok> <tok cat="NN">decline</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">site</tok> <tok cat="NN">alpha-</tok> <cons cat="NP" ref="i9" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="NP" id="i9"><cons cat="NP" null="QSTN"></cons><tok cat="JJ">beta-binding</tok> <tok cat="NNS">activities</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1035227309@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="JJ">CD4+</tok> <cons cat="NP" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">CD8+</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="VP"><tok cat="VBP">differ</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="JJ">beta-binding</tok> <tok cat="NNS">profiles</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i10"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i10" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">explain</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP"><tok cat="RBR">more</tok> <tok cat="JJ">pronounced</tok></cons> <tok cat="NN">down-regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CD28</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">senescent</tok> <tok cat="JJ">CD8+</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1035227310@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="FW">In</tok> <tok cat="FW">vivo</tok></cons> <cons cat="NP" role="SBJ"><tok cat="VBN">expanded</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">CD4+CD28null</tok> <cons cat="NP" ref="i11" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">CD8+CD28null</tok> <cons cat="NP" ref="i11" null="RNR"></cons></cons><cons cat="NP" id="i11"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">uniformly</tok></cons> <cons cat="VP"><tok cat="VBP">lack</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">alpha-</tok> <cons cat="NP" ref="i12" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="NP" id="i12"><tok cat="JJ">beta- bound</tok> <tok cat="NNS">complexes</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">resembling</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">pattern</tok></cons> <cons cat="VP"><tok cat="VBN">seen</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="RB">chronically</tok> <tok cat="VBN">activated</tok> <tok cat="NNS">cells</tok></cons></cons> <tok cat="CC">and</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">senescent</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1035227901@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">CD28</tok> <tok cat="NN">costimulation</tok></cons> <cons cat="VP"><tok cat="VBZ">augments</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">secretion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">activated</tok> <tok cat="NN">lamina</tok> <tok cat="NN">propria</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">increasing</tok> <cons cat="NP"><tok cat="NN">mRNA</tok> <tok cat="NN">stability</tok></cons> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">enhancing</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">gene</tok> <tok cat="NN">transactivation</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1035227902@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" id="i1"><tok cat="DT">The</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="VP"><tok cat="VBG">leading</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">lamina</tok> <tok cat="NN">propria</tok> <tok cat="LRB">(</tok><tok cat="NN">LP</tok><tok cat="RRB">)</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">different</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1035227903@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="NN">LP</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">exhibit</tok> <cons cat="NP"><tok cat="VBN">enhanced</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">secretion</tok></cons> <cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i2"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" id="i4" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">CD2</tok> <tok cat="NN">pathway</tok></cons></cons><cons cat="ADVP" ref="i2" null="T"></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1035227904@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Coligation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CD28</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">leads</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">synergistic</tok> <tok cat="NN">enhancement</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">secretion</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1035227905@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Previous</tok> <tok cat="NNS">studies</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">characterized</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">CD28</tok> <tok cat="NN">augmentation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">TCR-mediated</tok> <tok cat="NN">signaling</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">promoter</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD28</tok> <tok cat="NN">response</tok> <tok cat="NN">element</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">CD28RE</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">along</tok> <tok cat="IN">with</tok> <cons cat="NP"><tok cat="VBN">enhanced</tok> <tok cat="NN">mRNA</tok> <tok cat="NN">stability</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1035227906@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">study</tok></cons> <cons cat="VP"><tok cat="VBD">characterized</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">molecular</tok> <tok cat="NNS">events</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD28</tok> <tok cat="NN">costimulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">LP</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">LPMC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1035227907@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">LPMC</tok></cons> <cons cat="VP"><tok cat="VBD">exhibited</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">CD28</tok> <tok cat="NN">costimulation</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S" func="ADV"><cons cat="NP" id="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">compared</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD2</tok></cons> <cons cat="ADJP"><tok cat="RB">alone</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1035227908@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="NN">IL-2</tok> <tok cat="NN">secretion</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">paralleled</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">mRNA</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBG">resulting</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="VBN">enhanced</tok> <tok cat="NN">IL-2</tok> <tok cat="NN">mRNA</tok> <tok cat="NN">stability</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1035227909@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">contrast</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">PBMC</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">EMSA</tok></cons> <cons cat="VP"><tok cat="VBD">revealed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">CD28</tok> <tok cat="NN">coligation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">CD2-activated</tok> <tok cat="NN">LPMC</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">result</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="VBN">increased</tok> <tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">trans-factors</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">CD28RE</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">nor</tok> <tok cat="VBD">did</tok> <cons cat="NP" role="SBJ"><tok cat="NN">Western</tok> <tok cat="NNS">blots</tok></cons> <cons cat="VP"><tok cat="VB">detect</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">changes</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">I-kappaBalpha</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">I-kappaBbeta</tok></cons></cons> <tok cat="NNS">levels</tok></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="VBG">following</tok> <cons cat="NP"><tok cat="NN">CD28</tok> <tok cat="NN">coligation</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1035227910@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i8" role="SBJ"><tok cat="NN">CD28</tok> <tok cat="NN">coligation</tok></cons> <cons cat="VP"><tok cat="VBZ">fails</tok> <cons cat="S"><cons cat="NP" ref="i8" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">enhance</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">promoter-reporter</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">RE/AP</tok> <tok cat="NN">construct</tok> <tok cat="NN">expression</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">CD2-activated</tok> <tok cat="NN">LPMC</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1035227911@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBN">reported</tok> <cons cat="NP" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">herein</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">molecular</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CD28</tok> <tok cat="NN">cosignaling</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">secretion</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">LP</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">unique</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">that</tok> <tok cat="NN">compartment</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">differ</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="VP"><tok cat="VBN">seen</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1035227912@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">observations</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">biological</tok> <tok cat="NN">significance</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">different</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">initiation</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">maintenance</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cytokine</tok> <tok cat="NN">repertoire</tok></cons> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">mucosa</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1035662901@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Glucocorticoid</tok> <tok cat="NNS">receptors</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">anorexia</tok> <tok cat="NN">nervosa</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Cushing</tok><tok cat="POS">'s</tok> <tok cat="NN">disease</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@10@@oe@16-12-2010 1035662902@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">BACKGROUND</tok></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">Patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">anorexia</tok> <tok cat="NN">nervosa</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">do</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">display</tok> <cons cat="NP"><tok cat="JJ">cushingoid</tok> <tok cat="NNS">features</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">spite</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">elevated</tok> <tok cat="NN">cortisol</tok> <tok cat="NN">plasma</tok> <tok cat="NNS">levels</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1035662903@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" id="i1" role="SBJ"><tok cat="IN">Whether</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">cortisol</tok> <tok cat="NN">resistance</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="VBN">reduced</tok> <tok cat="NN">availability</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">metabolic</tok> <tok cat="NNS">substrates</tok></cons></cons></cons> <cons cat="ADJP"><tok cat="JJ">necessary</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">develop</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">glucocorticoids</tok></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">responsible</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">this</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">established</tok><cons cat="NP" ref="i1" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1035662904@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">METHODS</tok></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i5" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="CD">Twenty-two</tok> <tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">severe</tok> <tok cat="JJ">restrictive</tok> <tok cat="NN">anorexia</tok> <tok cat="NN">nervosa</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">10</tok> <tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">active</tok> <tok cat="NN">Cushing</tok><tok cat="POS">'s</tok> <tok cat="NN">disease</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">24</tok> <tok cat="JJ">healthy</tok> <tok cat="NNS">volunteers</tok></cons> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">psychiatric</tok> <tok cat="NNS">disorders</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">mood</tok> <tok cat="NNS">alterations</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">investigated</tok><cons cat="NP" ref="i5" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1035662905@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="NN">Glucocorticoid</tok> <tok cat="NN">receptor</tok> <tok cat="NNS">characteristics</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">examined</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">mononuclear</tok> <tok cat="NNS">leukocytes</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">measuring</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">[3H]dexamethasone</tok> <tok cat="NN">binding</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">dexamethasone</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">[3H]thymidine</tok> <tok cat="NN">incorporation</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i7"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">represents</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">index</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NN">synthesis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1035662906@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">RESULTS</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">number</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">glucocorticoid</tok> <tok cat="NNS">receptors</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">mononuclear</tok> <tok cat="NNS">leukocytes</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">MNL</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">comparable</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">anorexia</tok> <tok cat="NN">nervosa</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">active</tok> <tok cat="NN">Cushing</tok><tok cat="POS">'s</tok> <tok cat="NN">disease</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NNS">subjects</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">binding</tok> <tok cat="NN">capacity</tok> <tok cat="CD">3.3</tok> <tok cat="CC">+/-</tok> <tok cat="CD">0.23</tok></cons> <tok cat="CC">vs.</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="QP"><tok cat="CD">3.7</tok> <tok cat="CC">+/-</tok> <tok cat="CD">0.30</tok></cons> <cons cat="NP" ref="i8" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><cons cat="QP"><tok cat="CD">3.5</tok> <tok cat="CC">+/-</tok> <tok cat="CD">0.20</tok></cons> <cons cat="NP" ref="i8" null="RNR"></cons></cons><cons cat="NP" id="i8"><tok cat="NN">fmol/10(6)</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@49@@oe@16-12-2010 1035662907@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Conversely</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i9" role="SBJ"><tok cat="NN">glucocorticoid</tok> <tok cat="NN">receptor</tok> <tok cat="NN">affinity</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP" syn="COOD"><cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBN">decreased</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">anorexia</tok> <tok cat="NN">nervosa</tok></cons></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">Cushing</tok><tok cat="POS">'s</tok> <tok cat="NNS">patients</tok></cons></cons></cons> <cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="TO">to</tok> <tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">dissociation</tok> <tok cat="NN">constant</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">4.0</tok> <tok cat="CC">+/-</tok> <tok cat="CD">0.31</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="CD">4.1</tok> <tok cat="CC">+/-</tok> <tok cat="CD">0.34</tok></cons></cons></cons> <tok cat="CC">vs.</tok> <cons cat="NP"><cons cat="QP"><tok cat="CD">2.9</tok> <tok cat="CC">+/-</tok> <tok cat="CD">0.29</tok></cons> <tok cat="NN">nmol/L</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">p</tok></cons> <cons cat="VP"><tok cat="JJR"><</tok> <cons cat="NP"><tok cat="CD">.001</tok></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">inversely</tok></cons> <cons cat="VP"><tok cat="VBN">correlated</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">urinary</tok> <tok cat="JJ">free</tok> <tok cat="NN">cortisol</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">both</tok> <tok cat="NNS">groups</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">patients</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@58@@oe@16-12-2010 1035662908@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i10" role="SBJ"><cons cat="NP"><tok cat="JJ">Basal</tok> <tok cat="NN">[3H]thymidine</tok> <tok cat="NN">incorporation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">MNL</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBN">reduced</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">anorexia</tok> <tok cat="NN">nervosa</tok></cons></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">Cushing</tok><tok cat="POS">'s</tok> <tok cat="NNS">patients</tok></cons></cons></cons> <cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">p</tok></cons> <cons cat="VP"><tok cat="JJR"><</tok> <cons cat="NP"><tok cat="CD">.001</tok></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="UCP" syn="COOD"><cons cat="VP"><tok cat="VBN">diminished</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">dexamethasone</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">extent</tok></cons> <cons cat="ADJP"><tok cat="JJ">similar</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">anorexia</tok> <tok cat="NN">nervosa</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="ADJP" role="PRD"><cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">p</tok></cons> <cons cat="VP"><tok cat="JJR"><</tok> <cons cat="NP"><tok cat="CD">.001</tok></cons></cons></cons><tok cat="RRB">)</tok></cons> <cons cat="ADJP"><tok cat="RBR">less</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Cushing</tok><tok cat="POS">'s</tok> <tok cat="NN">disease</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@60@@oe@16-12-2010 1035662909@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">anorexia</tok> <tok cat="NN">nervosa</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i11" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">incorporation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">[3H]thymidine</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">MNL</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">inversely</tok></cons> <cons cat="VP"><tok cat="VBN">correlated</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">urinary</tok> <tok cat="JJ">free</tok> <tok cat="NN">cortisol</tok> <tok cat="NNS">levels</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1035662910@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">CONCLUSIONS</tok></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">lack</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">cushingoid</tok> <tok cat="NNS">features</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">anorexia</tok> <tok cat="NN">nervosa</tok></cons></cons></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">ascribable</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="VBN">reduced</tok> <tok cat="NN">sensitivity</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NNS">glucocorticoids</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RBR">more</tok> <tok cat="RB">likely</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">due</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">paucity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">metabolic</tok> <tok cat="NNS">substrates</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1035781801@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Latent</tok> <tok cat="NN">membrane</tok> <tok cat="NN">protein</tok> <tok cat="CD">1</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">Epstein-Barr</tok> <tok cat="NN">virus</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">interacts</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">JAK3</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">activates</tok> <cons cat="NP"><tok cat="NN">STAT</tok> <tok cat="NNS">proteins</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1035781802@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="JJ">Latent</tok> <tok cat="NN">membrane</tok> <tok cat="NN">protein</tok> <tok cat="CD">1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">LMP1</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">acts</tok> <cons cat="PP"><tok cat="IN">like</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="RB">permanently</tok> <tok cat="VBN">activated</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">TNF</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="NN">-receptor</tok> <tok cat="NN">superfamily</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">absolutely</tok></cons> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NN">cell</tok> <tok cat="NN">immortalization</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="JJ">Epstein-Barr</tok> <tok cat="NN">virus</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1035781803@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">Molecular</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">biochemical</tok></cons></cons> <tok cat="NNS">approaches</tok></cons> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">LMP1</tok></cons> <cons cat="VP"><tok cat="VBZ">usurps</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cellular</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="VP"><tok cat="VBG">resulting</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><tok cat="CD">two</tok> <tok cat="JJ">C-terminal</tok> <tok cat="VBG">activating</tok> <tok cat="NNS">regions</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1035781804@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="ADVP"><tok cat="RB">here</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">third</tok> <tok cat="NN">region</tok></cons> <cons cat="VP"><tok cat="VBG">encompassing</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">proline</tok> <tok cat="JJ">rich</tok> <tok cat="NN">sequence</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="CD">33</tok> <tok cat="NN">bp</tok> <tok cat="JJ">repetitive</tok> <tok cat="NN">stretch</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">LMP1</tok><tok cat="POS">'s</tok></cons> <tok cat="NN">C-terminus</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Janus</tok> <tok cat="NN">kinase</tok> <tok cat="CD">3</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">JAK3</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1035781805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">LMP1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">JAK3</tok></cons></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">leads</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">enhanced</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">auto/transphosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">JAK3</tok></cons></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">within</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">minutes</tok></cons> <cons cat="PP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">crosslinking</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">conditional</tok> <tok cat="NN">NGF-R:LMP1</tok> <tok cat="NN">chimera</tok></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">prerequisite</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1035781806@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">reveal</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="VBG">activating</tok> <tok cat="NN">region</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">LMP1</tok> <tok cat="NN">C-terminus</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">identify</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">JAK/STAT</tok> <tok cat="NN">pathway</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">target</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">this</tok> <tok cat="JJ">viral</tok> <tok cat="JJ">integral</tok> <tok cat="NN">membrane</tok> <tok cat="NN">protein</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1035782001@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="VP"><tok cat="NN">Repression</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Ikaros</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Aiolos</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="NN">histone</tok> <tok cat="NN">deacetylase</tok> <tok cat="NNS">complexes</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1035782002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">lymphoid</tok> <tok cat="JJ">lineage-determining</tok> <tok cat="NNS">factors</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Ikaros</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Aiolos</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">function</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="JJ">strong</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NNS">repressors</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1035782003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">function</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="CD">two</tok> <tok cat="NN">repression</tok> <tok cat="NNS">domains</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">dependent</tok> <cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">promoter</tok> <tok cat="NN">context</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">type</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1035782004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">Repression</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">Ikaros</tok> <tok cat="NNS">proteins</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">correlates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">hypo-acetylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">core</tok> <tok cat="NNS">histones</tok></cons></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="NN">promoter</tok> <tok cat="NNS">sites</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">relieved</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">histone</tok> <tok cat="NN">deacetylase</tok> <tok cat="NNS">inhibitors</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1035782005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><cons cat="ADJP" role="PRD"><tok cat="JJ">Consistent</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">findings</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">Ikaros</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">repression</tok> <tok cat="NNS">domains</tok></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">interact</tok> <cons cat="ADVP" syn="COOD"><cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vivo</tok></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">mSin3</tok> <tok cat="NN">family</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">co-repressors</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">bind</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">histone</tok> <tok cat="NNS">deacetylases</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1035782006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">Based</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">these</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">our</tok> <tok cat="JJ">recent</tok> <tok cat="NNS">findings</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">associations</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Ikaros</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Mi-2-HDAC</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">propose</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NN">Ikaros</tok> <tok cat="NN">family</tok> <tok cat="NNS">members</tok></cons> <cons cat="VP"><tok cat="VBP">modulate</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="NN">lymphocyte</tok> <tok cat="NN">development</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">recruiting</tok> <cons cat="NP"><tok cat="JJ">distinct</tok> <tok cat="NN">histone</tok> <tok cat="NN">deacetylase</tok> <tok cat="NNS">complexes</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">specific</tok> <tok cat="NNS">promoters</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1035802801@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">20-Epi</tok> <tok cat="NNS">analogues</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">1,25-dihydroxyvitamin</tok> <tok cat="NN">D3</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP" role="PRD"><cons cat="NP"><cons cat="ADJP"><tok cat="RB">highly</tok> <tok cat="JJ">potent</tok></cons> <tok cat="NNS">inducers</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">DRIP</tok> <tok cat="NN">coactivator</tok> <tok cat="NN">complex</tok></cons> <cons cat="VP"><tok cat="NN">binding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">vitamin</tok> <tok cat="NN">D3</tok> <tok cat="NN">receptor</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1035802802@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">1,25-Dihydroxyvitamin</tok> <tok cat="NN">D3</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">1,25(OH)2D3</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">major</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">stimulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">bone</tok> <tok cat="NN">growth</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">mineralization</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">intestinal</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">calcium</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">phosphate</tok></cons></cons> <tok cat="NN">absorption</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBZ">acts</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">general</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">cellular</tok> <tok cat="NN">proliferation</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1035802803@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Several</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">new</tok></cons><tok cat="COMMA">,</tok> <cons cat="ADJP"><tok cat="RB">clinically</tok> <tok cat="JJ">relevant</tok></cons></cons> <tok cat="NNS">compounds</tok></cons> <cons cat="VP"><tok cat="VBP">dissociate</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">antiproliferative</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">calcemic</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NNS">activities</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">1,25(OH)2D3</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">basis</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">this</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="ADVP"><tok cat="RB">clearly</tok></cons> <cons cat="VP"><tok cat="VBN">elucidated</tok><cons cat="NP" ref="i2" null="NONE"></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1035802804@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">tested</tok> <cons cat="SBAR"><tok cat="IN">whether</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">potency</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">one</tok> <tok cat="NN">class</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">compounds</tok></cons><cons cat="PRN"><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">20-epi</tok> <tok cat="NNS">analogues</tok></cons><tok cat="COMMA">,</tok></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3" null="ZERO"></cons><cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><tok cat="JJ">myeloid</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="PP" role="PRD"><tok cat="IN">because</tok> <tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">direct</tok> <tok cat="JJ">molecular</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">vitamin</tok> <tok cat="NN">D</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">VDR</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1035802805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">report</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="CD">two</tok> <tok cat="NN">20-epi</tok> <tok cat="NNS">analogues</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">MC1627</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">MC1288</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">differentiation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">transcription</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">p21</tok></cons><cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Waf1</tok></cons><tok cat="COMMA">,</tok><cons cat="NP"><tok cat="NN">Cip1</tok></cons></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">key</tok> <tok cat="NN">VDR</tok> <tok cat="NN">target</tok> <tok cat="NN">gene</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">growth</tok> <tok cat="NN">inhibition</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">concentration</tok> <cons cat="ADJP"><cons cat="ADJP"><tok cat="RB">100-fold</tok> <tok cat="JJR">lower</tok></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">that</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">1,25(OH)2D3</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1035802806@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">compared</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">sensitivity</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">analogue</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">VDR</tok> <tok cat="NN">interacting</tok> <tok cat="NNS">proteins</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">RXR</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">GRIP-1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">DRIP205</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">subunit</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">DRIP</tok> <tok cat="NN">coactivator</tok> <tok cat="NN">complex</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1035802807@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" id="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">Compared</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">VDR</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">RXR</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">GRIP-1</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">differentiation</tok> <tok cat="NN">dose-response</tok></cons> <cons cat="ADVP"><tok cat="JJS">most</tok> <tok cat="RB">closely</tok></cons> <cons cat="VP"><tok cat="VBD">correlated</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">ligand-dependent</tok> <tok cat="NN">recruitment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">DRIP</tok> <tok cat="NN">coactivator</tok> <tok cat="NN">complex</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">VDR</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ability</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">receptor</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">cell-free</tok> <tok cat="NN">system</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1035802808@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">provide</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">compelling</tok> <tok cat="NNS">links</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">efficiency</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">20-epi</tok> <tok cat="NN">analogue</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">inducing</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">VDR/DRIP</tok> <tok cat="NNS">interactions</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">transactivation</tok> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="VBN">enhanced</tok> <tok cat="NN">ability</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><tok cat="JJ">cellular</tok> <tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1035815401@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">New</tok> <tok cat="JJ">immunosuppressive</tok> <tok cat="NN">drug</tok></cons> <cons cat="NP"><tok cat="NN">PNU156804</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">blocks</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">IL-2-dependent</tok> <tok cat="NN">proliferation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NN">activation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1035815402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="ADVP"><tok cat="RB">previously</tok></cons> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">drug</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">undecylprodigiosin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">UP</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">blocks</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">lymphocyte</tok> <tok cat="NN">proliferation</tok></cons> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1035815403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="ADVP"><tok cat="RB">now</tok></cons> <cons cat="VP"><tok cat="VBN">investigated</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">mechanism</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">action</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">new</tok> <tok cat="NN">analogue</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">UP</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">PNU156804</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">shows</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <cons cat="ADJP"><tok cat="RBR">more</tok> <tok cat="JJ">favorable</tok></cons> <tok cat="NN">activity</tok> <tok cat="NN">profile</tok></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">UP</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">mice</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1035815404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="ADVP"><tok cat="RB">here</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">biological</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PNU156804</tok></cons></cons> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">indistinguishable</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">UP</tok></cons></cons></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PNU156804</tok></cons> <cons cat="VP"><tok cat="VBZ">blocks</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">proliferation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">mid-late</tok> <tok cat="NN">G1</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">as</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">determined</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">cycle</tok> <tok cat="NN">analysis</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">cyclins</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">cyclin-dependent</tok> <tok cat="NNS">kinases</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">retinoblastoma</tok> <tok cat="NN">phosphorylation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1035815405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PNU156804</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">block</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="DT">either</tok> <cons cat="NP"><tok cat="NN">IL-2</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">IL-2R</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">alpha-</tok> <cons cat="NP" ref="i4" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="NP" id="i4"><tok cat="NNS">gamma-chains</tok></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><tok cat="JJ">IL-2-dependent</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">proliferation</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1035815406@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">investigated</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">several</tok> <tok cat="JJ">molecular</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" id="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="S"><cons cat="NP" ref="i6" id="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1035815407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PNU156804</tok></cons> <cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">inhibit</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">c-myc</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">bcl-2</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><cons cat="NP" id="i8"><tok cat="NN">mRNA</tok> <tok cat="NN">induction</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1035815408@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">On</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">other</tok> <tok cat="NN">hand</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">PNU156804</tok></cons> <cons cat="ADVP"><tok cat="RB">efficiently</tok></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons><cons cat="NP" id="i9"><tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1035815409@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">PNU156804</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">activation</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="PP" role="PRD"><tok cat="JJ">due</tok> <tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">degradation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">I</tok> <tok cat="NN">kappa</tok> <tok cat="NN">B-alpha</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">I</tok> <tok cat="NN">kappa</tok> <tok cat="NN">B-beta</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1035815410@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S"><cons cat="NP" id="i10" role="SBJ"><tok cat="NN">PNU156804</tok> <tok cat="NN">action</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">restricted</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">pathways</tok></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">PMA</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><cons cat="NP"><tok cat="VBZ">blocks</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="DT">that</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">CD40</tok> <tok cat="NN">cross-linking</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1035815411@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">conclude</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">prodigiosin</tok> <tok cat="NN">family</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">immunosuppressants</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">new</tok> <tok cat="NN">family</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">molecules</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i13"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i13" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">show</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="NN">target</tok> <tok cat="NN">specificity</tok></cons> <cons cat="ADJP"><tok cat="RB">clearly</tok> <tok cat="JJ">distinct</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">that</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="JJ">immunosuppressive</tok> <tok cat="NNS">drugs</tok></cons> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">cyclosporin</tok> <tok cat="NN">A</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">FK506</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">rapamycin</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1035817301@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-12</tok></cons> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">IFN</tok> <tok cat="NN">regulating</tok> <tok cat="NN">factor-1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IRF-1</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NK</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">T</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><cons cat="NP" id="i8"><tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1035817302@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-12</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">critical</tok> <tok cat="JJ">immunoregulatory</tok> <tok cat="NN">cytokine</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">promotes</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">cell-mediated</tok> <tok cat="JJ">immune</tok> <tok cat="NNS">responses</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">naive</tok> <tok cat="JJ">CD4+</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">Th1</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok> <cons cat="S"><cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><cons cat="ADJP"><tok cat="RB">relatively</tok> <tok cat="JJ">few</tok></cons> <tok cat="NN">IL-12</tok> <tok cat="NN">target</tok> <tok cat="NNS">genes</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">identified</tok><cons cat="NP" ref="i2" null="NONE"></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1035817303@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="ADVP"><tok cat="RBR">better</tok></cons> <cons cat="VP"><tok cat="VB">clarify</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">basis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-12</tok> <tok cat="NN">action</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i9" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">set</tok> <tok cat="RP">out</tok> <cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">characterize</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">genes</tok></cons> <cons cat="VP"><tok cat="VBN">up-regulated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">IL-12</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">first</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">contrasting</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-12-</tok> <cons cat="NP" ref="i10" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="NP" id="i10"><tok cat="JJ">IFN-alpha-inducible</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1035817304@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">identified</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">several</tok> <tok cat="NNS">genes</tok></cons> <cons cat="VP"><tok cat="VBN">up-regulated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-12</tok></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">namely</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">MIP-1alpha</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">MIP-1beta</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-1RA</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IFN</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">factor-1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IRF-1</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1035817305@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IRF-1</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="VP"><tok cat="VBN">regulated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">IFNs</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">essential</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">Th1</tok> <tok cat="NNS">responses</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1035817306@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-12</tok></cons> <cons cat="ADVP"><tok cat="RB">directly</tok></cons> <cons cat="VP"><tok cat="VBZ">up-regulates</tok> <cons cat="NP"><tok cat="NN">IRF-1</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">same</tok> <tok cat="NN">extent</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IFN-alpha</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">human</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">NK</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1035817307@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-12</tok></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">direct</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">IRF-1</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">effect</tok></cons> <cons cat="VP"><tok cat="RB">not</tok> <tok cat="VBN">mediated</tok> <cons cat="NP" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">indirectly</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IFN-gamma</tok> <tok cat="NN">production</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1035817308@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">IL-2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-12</tok></cons></cons> <cons cat="ADVP"><tok cat="RB">synergistically</tok></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><tok cat="NN">IRF-1</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">IFN-alpha</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-12</tok></cons></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok><cons cat="VP" null="QSTN"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1035817309@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">participation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT4</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IRF-1</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">demonstrated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="CD">two</tok> <tok cat="NNS">ways</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1035817310@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="ADVP"><tok cat="RB">First</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><tok cat="NN">STAT4</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">IL-12-dependent</tok> <tok cat="NN">transactivation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">IRF-1</tok> <tok cat="NN">reporter</tok> <tok cat="NN">construct</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">second</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="NN">STAT4</tok></cons> <cons cat="VP"><tok cat="VBG">binding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IRF-1</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="NN">EMSA</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1035817311@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">contrast</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">IL-12</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><tok cat="DT">no</tok> <tok cat="NN">up-regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IRF-1</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">IL-4-stimulated</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-4</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">block</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">IL-12-dependent</tok> <tok cat="NN">up-regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IRF-1</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1035817312@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="ADVP"><tok cat="RB">Therefore</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IRF-1</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">important</tok> <tok cat="NN">contributor</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">IL-12</tok> <tok cat="NN">signaling</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">speculate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">defective</tok> <tok cat="NN">IL-12</tok> <tok cat="NNS">responses</tok></cons> <cons cat="VP"><tok cat="VBN">seen</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">IRF-1-/-</tok> <tok cat="NNS">mice</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">might</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">attributable</tok><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">part</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@39@@oe@16-12-2010 1035817801@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="JJ">Multiple</tok> <tok cat="NN">NF-ATc</tok> <tok cat="NNS">isoforms</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">individual</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NNS">properties</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">synthesized</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1035817802@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="NP"><tok cat="NN">NF-ATc</tok></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">controls</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">embryonic</tok> <tok cat="JJ">cardiac</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="CD">three</tok> <tok cat="JJ">prominent</tok> <tok cat="NNS">isoforms</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1035817803@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><cons cat="NP"><tok cat="JJ">due</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">alternative</tok> <tok cat="NN">splice/polyadenylation</tok> <tok cat="NNS">events</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">lead</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">predominant</tok> <tok cat="NN">synthesis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="CD">two</tok> <tok cat="JJ">long</tok> <tok cat="NNS">isoforms</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">naive</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJR">shorter</tok> <tok cat="NN">NF-ATc</tok> <tok cat="NN">isoform</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">effector</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1035817804@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">Whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="ADJP"><tok cat="RB">previously</tok> <tok cat="VBN">described</tok></cons> <tok cat="NN">isoform</tok> <tok cat="NN">NF-ATc/A</tok></cons> <cons cat="VP"><tok cat="VBZ">contains</tok> <cons cat="NP"><tok cat="DT">a</tok> <cons cat="ADJP"><tok cat="RB">relatively</tok> <tok cat="JJ">short</tok></cons> <tok cat="NN">C</tok> <tok cat="NN">terminus</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJR">longer</tok> <tok cat="NNS">isoforms</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">B</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">C</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBP">span</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">extra</tok> <tok cat="JJ">C-terminal</tok> <tok cat="NNS">peptides</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">128</tok> <cons cat="NP" ref="i11" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="CD">246</tok> <cons cat="NP" ref="i11" null="RNR"></cons></cons><cons cat="NP" id="i11"><tok cat="NN">aa</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">respectively</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1035817805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="ADVP"><tok cat="RB">here</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">strong</tok> <tok cat="JJ">N-terminal</tok> <tok cat="NN">trans-activation</tok> <tok cat="NN">domain</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">TAD-A</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">common</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">all</tok> <tok cat="CD">three</tok> <tok cat="NN">NF-ATc</tok> <tok cat="NNS">isoforms</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">NF-ATc/C</tok></cons> <cons cat="VP"><tok cat="VBZ">contains</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">second</tok> <tok cat="NN">trans-activation</tok> <tok cat="NN">domain</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">TAD-B</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">C-terminal</tok> <tok cat="NN">peptide</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1035817806@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Various</tok> <tok cat="NNS">stimuli</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">induce</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TAD-A</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBP">enhance</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TAD-B</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="PP"><tok cat="IN">unlike</tok> <cons cat="NP"><tok cat="NN">TAD-A</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7" role="SBJ"><tok cat="NN">TAD-B</tok></cons> <cons cat="VP"><tok cat="VBZ">remains</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">unphosphorylated</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">protein</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">12-O-tetradecanoyl</tok> <tok cat="NN">12-phorbol</tok> <tok cat="JJ">13-acetate-stimulated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1035817807@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJR">shorter</tok> <tok cat="JJ">C-terminal</tok> <tok cat="NN">peptide</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">isoform</tok> <tok cat="NN">NF-ATc/B</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">exerts</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">suppressive</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">effect</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1035817808@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">These</tok> <tok cat="NNS">properties</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NF-ATc/B</tok></cons> <tok cat="CC">and</tok><cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">- C</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">might</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="PP" role="PRD"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">importance</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">naive</tok> <tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i9"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" syn="COOD" id="i10" role="SBJ"><cons cat="NP"><tok cat="NN">NF-ATc/B</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">-C</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">predominantly</tok></cons> <cons cat="VP"><tok cat="VBN">synthesized</tok><cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP" ref="i9" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1035875601@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Transcriptional</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">lymphocyte</tok> <tok cat="NN">development</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">function</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@9@@oe@16-12-2010 1035875602@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP" syn="COOD"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="NN">development</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">function</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">regulated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">tightly</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">signal</tok> <tok cat="NN">transduction</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">include</tok> <cons cat="NP" syn="COOD"><tok cat="JJ">specific</tok> <cons cat="NP"><tok cat="JJ">cell-surface</tok> <tok cat="NNS">receptors</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">intracellular</tok> <tok cat="VBG">signaling</tok> <tok cat="NNS">molecules</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1035875603@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP" adv="TMP"><tok cat="IN">Since</tok> <cons cat="NP"><tok cat="CD">1988</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="JJ">several</tok> <tok cat="NNS">families</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="RB">functionally</tok> <tok cat="JJ">important</tok></cons> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">identified</tok><cons cat="NP" ref="i4" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1035875604@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok></cons> <cons cat="VP"><tok cat="VBP">include</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">Ikaros</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">LKLF</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">GATA3</tok> <tok cat="JJ">zinc-finger</tok> <tok cat="NNS">proteins</tok></cons></cons><tok cat="COLON">;</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">Ets</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">CREB/ATF</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B/Rel/NFAT</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons><tok cat="COLON">;</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Stat</tok> <tok cat="NNS">proteins</tok></cons><tok cat="COLON">;</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">HMG</tok> <tok cat="NN">box</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">LEF1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">TCF1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Sox4</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1035875605@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">review</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">summarize</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">our</tok> <tok cat="JJ">current</tok> <tok cat="NN">understanding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">development</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">function</tok></cons></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">particular</tok> <tok cat="NN">emphasis</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">results</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><tok cat="JJ">recent</tok> <cons cat="ADJP"><tok cat="NN">gene</tok> <tok cat="NN">targeting</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">transgenic</tok></cons></cons> <tok cat="NNS">experiments</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1035875606@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">increasing</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">our</tok> <tok cat="NN">understanding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">molecular</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">regulate</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">development</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">function</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">suggested</tok> <cons cat="NP"><tok cat="JJ">novel</tok> <tok cat="NNS">targets</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">genetic</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">pharmacological</tok></cons></cons> <tok cat="NN">manipulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">immunity</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1035876401@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Development</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">maturation</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">secondary</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">tissues</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@8@@oe@16-12-2010 1035876402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="DT">The</tok> <tok cat="JJ">secondary</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">tissues</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="JJ">located</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">strategic</tok> <tok cat="NNS">sites</tok></cons> <cons cat="SBAR"><cons cat="WHADVP" id="i3"><tok cat="WRB">where</tok></cons> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="JJ">foreign</tok> <tok cat="NNS">antigens</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADVP"><tok cat="RB">efficiently</tok></cons> <cons cat="VP"><tok cat="VBN">brought</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">together</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="UCP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">immune</tok> <tok cat="NN">system</tok> <tok cat="JJ">regulatory</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">effector</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><cons cat="NP" id="i5"><tok cat="NNS">cells</tok></cons></cons></cons><cons cat="ADVP" ref="i3" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1035876403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="VBN">organized</tok> <tok cat="NN">structure</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">secondary</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">tissues</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">thought</tok> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="NONE"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">enhance</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">sensitivity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">antigen</tok> <tok cat="NN">recognition</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">support</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">proper</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">activation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">maturation</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">antigen-responsive</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1035876404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">Although</tok> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="DT">a</tok> <tok cat="JJ">substantial</tok> <tok cat="NN">amount</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">about</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cellular</tok> <tok cat="NNS">elements</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i9"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">compose</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">lymphoid</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">nonlymphoid</tok></cons></cons> <tok cat="NNS">components</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">secondary</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">tissues</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i11" role="SBJ"><cons cat="NP" id="i10"><tok cat="NN">information</tok></cons> <cons cat="PP"><tok cat="VBG">concerning</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">signals</tok></cons> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><cons cat="WHNP" id="i12"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i12" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">control</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">development</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">tissues</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><cons cat="WHNP" id="i13"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i13" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">maintain</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">organized</tok> <tok cat="NN">tissue</tok> <tok cat="NN">microenvironment</tok></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">remain</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">undefined</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1035876405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">Studies</tok></cons> <cons cat="PP"><tok cat="IN">over</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">past</tok> <tok cat="JJ">few</tok> <tok cat="NNS">years</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">identified</tok> <cons cat="NP"><tok cat="NN">lymphotoxin</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">critical</tok> <tok cat="VBG">signaling</tok> <tok cat="NN">molecule</tok></cons> <cons cat="PP" syn="COOD"><cons cat="CONJP"><tok cat="RB">not</tok> <tok cat="RB">only</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">organogenesis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">secondary</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">tissues</tok></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">maintenance</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">aspects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">microarchitecture</tok></cons></cons></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">as</tok> <tok cat="RB">well</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1035876406@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i14" role="SBJ"><cons cat="NP" role="SBJ"><tok cat="JJ">Additional</tok> <tok cat="VBG">signaling</tok> <tok cat="NNS">molecules</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i15"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i15" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">contribute</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">formation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NN">tissue</tok> <tok cat="NN">structure</tok></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBG">being</tok> <cons cat="VP"><tok cat="VBN">identified</tok> <cons cat="NP" ref="i14" null="NONE"></cons><cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="VBG">accelerating</tok> <tok cat="NN">pace</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1035876407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i16" role="SBJ"><cons cat="NP"><tok cat="NNS">Analyses</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">mouse</tok> <tok cat="NNS">strains</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">congenital</tok> <tok cat="NNS">defects</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">different</tok> <tok cat="NNS">aspects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">secondary</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NN">tissue</tok> <tok cat="NN">development</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBG">beginning</tok> <cons cat="S"><cons cat="NP" ref="i16" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">clarify</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">tissues</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">immune</tok> <tok cat="NNS">responses</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">host</tok> <tok cat="NN">defense</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1035876408@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">review</tok></cons> <cons cat="VP"><tok cat="VBZ">focuses</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">studies</tok></cons> <cons cat="VP"><tok cat="VBG">defining</tok> <cons cat="NP"><cons cat="NP"><cons cat="ADJP"><tok cat="RB">recently</tok> <tok cat="VBN">identified</tok></cons> <tok cat="JJ">crucial</tok> <tok cat="NNS">signals</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">biogenesis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">secondary</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">organs</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">maintenance</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="JJ">proper</tok> <tok cat="NN">microarchitecture</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1035876409@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">It</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBZ">discusses</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">new</tok> <tok cat="NNS">insights</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="SBAR"><cons cat="WHADVP" id="i17"><tok cat="WRB">how</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">structure</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">tissues</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">supports</tok> <cons cat="NP"><tok cat="JJ">effective</tok> <tok cat="JJ">immune</tok> <tok cat="NNS">responses</tok></cons><cons cat="ADVP" ref="i17" null="T"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1035877501@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Selection</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">repertoire</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@7@@oe@16-12-2010 1035877502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">Advances</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">technology</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">allowed</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">manipulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">molecular</tok> <tok cat="NNS">interactions</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">shape</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">repertoire</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1035877503@GENIA Treebank@formal@@1@S@<cons cat="SINV"><cons cat="SBAR"><tok cat="IN">Although</tok> <cons cat="S"><cons cat="NP" ref="i2" id="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">recognized</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">fundamental</tok> <tok cat="NNS">aspects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">lymphocyte</tok> <tok cat="NN">development</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP" adv="TMP"><tok cat="RB">only</tok> <tok cat="RB">recently</tok></cons> <tok cat="VBP">have</tok> <cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="VP"><tok cat="VBG">governing</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">positive</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">negative</tok></cons></cons> <tok cat="NN">selection</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">examined</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">level</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1035877504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Positive</tok> <tok cat="NN">selection</tok></cons> <cons cat="VP"><tok cat="VBZ">refers</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">active</tok> <tok cat="NN">process</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">rescuing</tok> <cons cat="NP"><tok cat="JJ">MHC-restricted</tok> <tok cat="NNS">thymocytes</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="VBN">programmed</tok> <tok cat="NN">cell</tok> <tok cat="NN">death</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1035877505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Negative</tok> <tok cat="NN">selection</tok></cons> <cons cat="VP"><tok cat="VBZ">refers</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">deletion</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">inactivation</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="RB">potentially</tok> <tok cat="JJ">autoreactive</tok> <tok cat="NNS">thymocytes</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1035877506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">review</tok></cons> <cons cat="VP"><tok cat="VBZ">focuses</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">interactions</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="NN">thymocyte</tok> <tok cat="NN">maturation</tok></cons></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i7"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">define</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">repertoire</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">emphasis</tok></cons> <cons cat="VP"><tok cat="VBN">placed</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">current</tok> <tok cat="NN">literature</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">field</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1035901201@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="NN">Phorbol</tok> <tok cat="JJ">ester-induced</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">blocked</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">mitogen-activated</tok> <tok cat="NN">protein</tok> <tok cat="NN">kinase</tok> <tok cat="NN">kinase</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MEK</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">inhibitor</tok></cons> <cons cat="NP"><tok cat="NN">PD98059</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1035901202@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">purpose</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="S" role="PRD"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">evaluate</tok> <cons cat="SBAR"><tok cat="IN">whether</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">mitogen-activated</tok> <tok cat="NN">protein</tok> <tok cat="NN">kinase</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MAPK</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">signaling</tok> <tok cat="NN">pathway</tok></cons> <cons cat="VP"><tok cat="VBZ">contributes</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">12-O-tetradecanoylphorbol-13-acetate</tok> <tok cat="LRB">(</tok><tok cat="NN">TPA</tok><tok cat="RRB">)</tok><tok cat="JJ">-induced</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">human</tok> <tok cat="JJ">myeloblastic</tok> <tok cat="NN">leukemia</tok> <tok cat="NN">ML-1</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1035901203@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Upon</tok> <cons cat="NP"><tok cat="NN">TPA</tok> <tok cat="NN">treatment</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">ERK1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">ERK2</tok></cons></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">rapidly</tok></cons> <cons cat="VP"><tok cat="VBD">increased</tok><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">maximal</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP"><cons cat="QP"><tok cat="CD">1</tok> <tok cat="CC">and</tok> <tok cat="CD">3</tok></cons> <tok cat="NN">h</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR" adv="TMP"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">ERK2</tok> <tok cat="NN">protein</tok> <tok cat="NNS">levels</tok></cons> <cons cat="VP"><tok cat="VBD">remained</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">constant</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1035901204@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">JNK1</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok><cons cat="NP" ref="i2" null="NONE"></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">JNK1</tok> <tok cat="NN">protein</tok> <tok cat="NNS">levels</tok></cons> <cons cat="VP"><tok cat="VBG">increasing</tok> <cons cat="ADVP"><tok cat="RB">moderately</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">exposure</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">TPA</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1035901205@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Treatment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">PD98059</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">specific</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">mitogen-activated</tok> <tok cat="NN">protein</tok> <tok cat="NN">kinase</tok> <tok cat="NN">kinase</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MEK</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><tok cat="JJ">TPA-induced</tok> <tok cat="NN">ERK2</tok> <tok cat="NN">activity</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1035901206@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">PD98059</tok></cons> <cons cat="ADVP"><tok cat="RB">completely</tok></cons> <cons cat="VP"><tok cat="VBD">blocked</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">TPA-induced</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">ML-1</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">as</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">assessed</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">number</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">features</tok></cons> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP" id="i5"><tok cat="JJ">mononuclear</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">changes</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">morphology</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">nonspecific</tok> <tok cat="NN">esterase</tok> <tok cat="NN">activity</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">phagocytic</tok> <tok cat="NN">ability</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">NADPH</tok> <tok cat="NN">oxidase</tok> <tok cat="NN">activity</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">mitochondrial</tok> <tok cat="NN">respiration</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">c-jun</tok> <tok cat="NN">mRNA</tok> <tok cat="NN">inducibility</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@47@@oe@16-12-2010 1035901207@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">conclude</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">MEK/ERK</tok> <tok cat="NN">signaling</tok> <tok cat="NN">pathway</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">necessary</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">TPA-induced</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1035913801@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Immune</tok> <tok cat="NNS">functions</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">clinical</tok> <tok cat="NNS">parameters</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">hormone</tok> <tok cat="NN">receptor</tok> <tok cat="NN">status</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">breast</tok> <tok cat="NN">cancer</tok> <tok cat="NNS">patients</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1035913802@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">carried</tok> <tok cat="RP">out</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">detailed</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cellular</tok> <tok cat="JJ">immune</tok> <tok cat="NNS">functions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">breast</tok> <tok cat="NN">cancer</tok> <tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">comparison</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">healthy</tok> <tok cat="NNS">controls</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1035913803@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="JJ">possible</tok> <tok cat="NN">correlation</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">immune</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">clinical</tok></cons></cons> <tok cat="NNS">parameters</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="NP"><tok cat="VBN">analysed</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="CD">50</tok> <tok cat="NN">breast</tok> <tok cat="NN">cancer</tok> <tok cat="NNS">patients</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1035913804@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="JJ">Immune</tok> <tok cat="NNS">parameters</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">natural</tok> <tok cat="NN">killer</tok> <tok cat="NN">cell</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">lymphocyte</tok> <tok cat="NNS">functions</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">numbers</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBG">circulating</tok> <tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">analysed</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">clinical</tok> <tok cat="NNS">parameters</tok></cons> <cons cat="PP"><tok cat="VBG">comprising</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">tumour</tok> <tok cat="NN">burden</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">stage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">disease</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">hormone</tok> <tok cat="NNS">receptors</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">tumour</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1035913805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">In</tok> <tok cat="NN">order</tok> <tok cat="TO">to</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VB">analyse</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">immune</tok> <tok cat="NN">function</tok> <tok cat="NNS">data</tok></cons> <cons cat="ADVP"><tok cat="RB">effectively</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><tok cat="JJ">low</tok> <tok cat="NNS">responders</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">identified</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">stringent</tok> <tok cat="JJ">cut-off</tok> <tok cat="NNS">values</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1035913806@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><cons cat="ADJP"><tok cat="RB">Considerably</tok> <tok cat="JJR">higher</tok></cons> <tok cat="NNS">proportions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">low</tok> <tok cat="NNS">responders</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">among</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">patient</tok> <tok cat="NN">population</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1035913807@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Elevated</tok> <tok cat="NNS">numbers</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="VBG">circulating</tok> <tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">CD3-directed</tok> <tok cat="NN">cytolysis</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">correlated</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">oestrogen</tok> <tok cat="NNS">receptors</tok></cons> <cons cat="PP"><cons cat="ADVP"><tok cat="RB">independently</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">clinical/histological</tok> <tok cat="NNS">parameters</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1035945701@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="JJ">UV-induced</tok> <tok cat="NN">CYP1A1</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">tryptophan</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1035945702@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="NN">Induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">cytochrome</tok> <tok cat="NN">P-4501A1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">CYP1A1</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">activity</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">UV</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><cons cat="ADVP"><tok cat="RBR">earlier</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">animal</tok> <tok cat="NNS">studies</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">mechanism</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" id="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">has</tok> <tok cat="RB">not</tok> <cons cat="ADVP"><tok cat="RB">yet</tok></cons> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">resolved</tok><cons cat="NP" ref="i4" null="NONE"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1035945703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="JJ">previous</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">indicated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="VBN">formylated</tok> <tok cat="NNS">indolocarbazoles</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" id="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">formed</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">UV</tok> <tok cat="NN">irradiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">tryptophan</tok> <tok cat="NNS">solutions</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP" role="PRD"><cons cat="ADJP"><tok cat="RB">very</tok> <tok cat="JJ">potent</tok></cons> <tok cat="NN">Ah-receptor</tok> <tok cat="NNS">agonists</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1035945704@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">evaluate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">UV</tok> <tok cat="NN">light</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cytochrome</tok> <tok cat="NN">P4501A1</tok></cons> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">studied</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CYP1A1</tok> <tok cat="NN">mRNA</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">UV</tok> <tok cat="NN">irradiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="VBN">cultured</tok> <tok cat="JJ">human</tok> <tok cat="NNS">keratinocytes</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">HaCaT</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">primary</tok> <tok cat="JJ">human</tok> <tok cat="NN">blood</tok> <tok cat="NNS">lymphocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">mouse</tok> <tok cat="NN">Hepa-1</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@42@@oe@16-12-2010 1035945705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="DT">The</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">exposed</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">UV</tok> <tok cat="NN">light</tok></cons> <cons cat="VP"><tok cat="VBN">delivered</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">bank</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">6</tok> <tok cat="NN">Philips</tok> <tok cat="NN">TL20/12RS</tok> <tok cat="NN">sun</tok> <tok cat="NNS">lamps</tok></cons> <cons cat="VP"><tok cat="VBG">emitting</tok> <cons cat="ADVP"><tok cat="RB">primarily</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">UVB</tok> <tok cat="NN">range</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">presence</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">tryptophan</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1035945706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i10" role="SBJ"><tok cat="DT">A</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">semiquantitative</tok> <tok cat="NN">reverse</tok> <tok cat="JJ">transcriptase-linked</tok> <tok cat="NN">polymerase</tok> <tok cat="NN">chain</tok> <tok cat="NN">reaction</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">RT-PCR</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">treated</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1035945707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">CYP1A1</tok> <tok cat="NN">mRNA</tok> <tok cat="NN">level</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">UV</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">tryptophan</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJR">higher</tok> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">that</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">UV</tok></cons> <cons cat="ADJP"><tok cat="RB">alone</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">HaCaT</tok> <tok cat="NNS">cells</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">lymphocytes</tok></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">3</tok> <tok cat="NN">h</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">incubation</tok> <tok cat="JJ">post-UV</tok> <tok cat="NN">irradiation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1035945708@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">find</tok> <tok cat="RP">out</tok> <cons cat="SBAR"><tok cat="IN">if</tok> <cons cat="S"><cons cat="NP" id="i11" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">UV</tok> <tok cat="NN">light</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">caused</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">formation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">Ah</tok> <tok cat="NN">receptor</tok> <tok cat="NN">ligand</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" id="i12" role="SBJ"><cons cat="NP"><tok cat="NN">Hepa-1</tok> <tok cat="JJ">wild-type</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Ah</tok> <tok cat="NN">receptor</tok> <tok cat="JJ">deficient</tok> <tok cat="NN">c12</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">applied</tok><cons cat="NP" ref="i12" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1035945709@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Wild-type</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="JJ">wt</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">inducible</tok> <cons cat="PP" syn="COOD"><tok cat="CC">either</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">tryptophan</tok> <tok cat="NN">photoproduct</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="JJ">6-formylindolo</tok><tok cat="LRB">[</tok><tok cat="CD">3</tok><tok cat="COMMA">,</tok><tok cat="JJ">2-b</tok><tok cat="RRB">]</tok><tok cat="NN">carbazole</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">FICZ</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">UV-irradiation</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" id="i13" role="SBJ"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="RB">very</tok> <tok cat="JJ">low</tok></cons> <tok cat="CC">or</tok> <cons cat="ADJP"><tok cat="JJ">undetectable</tok></cons></cons> <tok cat="NNS">levels</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i13" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">c12</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1035945710@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok></cons> <cons cat="VP"><tok cat="VBZ">shows</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">FICZ</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">UV</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="NN">Ah</tok> <tok cat="NN">receptor</tok> <tok cat="JJ">dependent</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1035945711@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Together</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i14" role="SBJ"><cons cat="NP"><tok cat="JJ">UV-induced</tok> <tok cat="NN">CYP1A1</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">mammalian</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i14" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">Ah</tok> <tok cat="NN">receptor</tok> <tok cat="NN">ligand</tok></cons> <cons cat="VP"><tok cat="VBN">formed</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">tryptophan</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons></cons></cons>@@@@1@24@@oe@16-12-2010 1035945712@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Thus</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i15" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">photoproducts</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">tryptophan</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">suggested</tok> <cons cat="S"><cons cat="NP" ref="i15" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="NNS">mediators</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">light</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Ah</tok> <tok cat="NN">receptor</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">as</tok> <tok cat="JJ">such</tok></cons> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="MD">could</tok> <cons cat="VP"><tok cat="VB">have</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">light-regulated</tok> <tok cat="JJ">biological</tok> <tok cat="NNS">rhythms</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1035989401@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NNS">Effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">diesel</tok> <tok cat="JJ">organic</tok> <tok cat="NNS">extracts</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">chemokine</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1035989402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">BACKGROUND</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Polyaromatic</tok> <tok cat="NNS">hydrocarbons</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">PAHs</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">diesel</tok> <tok cat="NN">exhaust</tok> <tok cat="NNS">particles</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">DEPs</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">atmospheric</tok> <tok cat="JJ">urban</tok> <tok cat="NN">pollution</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1035989403@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="JJ">Such</tok> <tok cat="NNS">compounds</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">favor</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IgE</tok> <tok cat="NN">production</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">bronchial</tok> <tok cat="NN">hyperresponsiveness</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">airway</tok> <tok cat="NN">inflammation</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1035989404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NNS">Chemokines</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">group</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">chemotactic</tok> <tok cat="NNS">cytokines</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">recruitment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">inflammatory</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1035989405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">OBJECTIVE</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">investigated</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">DEP-PAHs</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">release</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">mRNA</tok> <tok cat="NN">expression</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-8</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">MCP-1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">RANTES</tok></cons></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">PBMCs</tok></cons> <cons cat="VP"><tok cat="VBN">obtained</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">healthy</tok> <tok cat="NNS">subjects</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1035989406@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="NP"><tok cat="NNS">METHODS</tok></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="NN">Protein</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">supernatants</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">assessed</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">ELISA</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NN">mRNA</tok> <tok cat="NN">expression</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">evaluated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="JJ">semiquantitative</tok> <tok cat="NN">RT-PCR</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1035989407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">RESULTS</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Secretion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-8</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">RANTES</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">increased</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dose-dependent</tok> <tok cat="NN">manner</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="VBG">increasing</tok> <tok cat="NNS">concentrations</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">DEP-PAHs</tok></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="NN">range</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">0.5</tok> <tok cat="NN">ng</tok> <cons cat="NP" null="QSTN"></cons></cons><tok cat="TO">to</tok> <cons cat="NP"><tok cat="CD">50</tok> <tok cat="NN">ng/mL</tok></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1035989408@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">On</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">contrary</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">release</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">MCP-1</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBN">inhibited</tok><cons cat="NP" ref="i6" null="NONE"></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dose-dependent</tok> <tok cat="NN">manner</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1035989409@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Messenger</tok> <tok cat="NN">RNA</tok> <tok cat="NN">production</tok> <tok cat="VBG">coding</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-8</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">RANTES</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">MCP-1</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">parallel</tok> <tok cat="NNS">variations</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">correspondent</tok> <tok cat="NNS">proteins</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1035989410@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">Effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">DEP-PAHs</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">became</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">significant</tok> <cons cat="PP" syn="COOD"><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="CD">7</tok> <tok cat="NNS">hours</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><cons cat="ADVP"><tok cat="IN">up</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">48</tok> <tok cat="NNS">hours</tok> <tok cat="NN">time</tok> <tok cat="NN">culture</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">MCP-1</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="PP"><cons cat="ADVP"><tok cat="IN">up</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">24</tok> <tok cat="NNS">hours</tok> <tok cat="NN">time</tok> <tok cat="NN">culture</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-8</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">RANTES</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1035989411@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">supernatants</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">DEP-PAH-activated</tok> <tok cat="NNS">cells</tok></cons></cons></cons><cons cat="PRN"><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">controls</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBD">exhibited</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <cons cat="ADJP"><tok cat="RB">significantly</tok> <tok cat="VBN">enhanced</tok></cons> <tok cat="JJ">chemotactic</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">neutrophils</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">eosinophils</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i7"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">pretreatment</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">anti-IL-8</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">anti-RANTES</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><cons cat="NP" id="i3"><tok cat="NN">neutralizing</tok> <tok cat="NNS">antibodies</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">respectively</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@39@@oe@16-12-2010 1035989412@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">CONCLUSION</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">chemokine</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">modulated</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NNS">DEP-PAHs</tok></cons></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">level</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">reinforcing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">idea</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i9" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">development</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">inflammatory</tok> <tok cat="NNS">reactions</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">might</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">affected</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">diesel</tok> <tok cat="NN">exhaust</tok> <tok cat="NN">emission</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1035989501@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">YY1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Oct1</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="NN">element</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">downregulates</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-5</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1035989502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">BACKGROUND</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" id="i2" role="SBJ"><tok cat="NN">IL-5</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">controls</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">development</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">eosinophilia</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="S"><cons cat="NP" ref="i2" id="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">pathogenesis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">allergic</tok> <tok cat="NNS">diseases</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1035989503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><tok cat="CC">both</tok> <cons cat="ADJP"><tok cat="JJ">atopic</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">nonatopic</tok></cons></cons> <tok cat="NN">asthma</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i4" role="SBJ"><tok cat="JJ">elevated</tok> <tok cat="NN">IL-5</tok></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">airways</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1035989504@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NN">IL-5</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">produced</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">mainly</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="VBN">activated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="PRPP">its</tok> <tok cat="NN">expression</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">regulated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">level</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1035989505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">OBJECTIVE</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">study</tok></cons> <cons cat="VP"><tok cat="VBZ">focuses</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">functional</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">IL-5</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">hIL-5</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">promoter</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">characterization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">cis -regulatory</tok> <tok cat="NNS">elements</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">suppression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-5</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1035989506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">METHODS</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="NNS">Methods</tok></cons> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">include</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">DNase</tok> <tok cat="CD">I</tok> <tok cat="NN">footprint</tok> <tok cat="NNS">assays</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">electrophoretic</tok> <tok cat="NN">mobility</tok> <tok cat="NN">shift</tok> <tok cat="NNS">assays</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">functional</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">mammalian</tok> <tok cat="NN">cell</tok> <tok cat="NN">transfection</tok></cons></cons></cons> <cons cat="PP"><tok cat="VBG">involving</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">deletion</tok> <tok cat="NN">analysis</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">site-directed</tok> <tok cat="NN">mutagenesis</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1035989507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">RESULTS</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">identified</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">5</tok> <tok cat="NN">protein</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok> <tok cat="NNS">regions</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">BRs</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="JJ">located</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">proximal</tok> <tok cat="NN">hIL-5</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1035989508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Functional</tok> <tok cat="NN">analysis</tok></cons> <cons cat="VP"><tok cat="VBZ">indicates</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="DT">the</tok> <tok cat="NNS">BRs</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">hIL-5</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1035989509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="CD">Two</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">regions</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">BR3</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">BR4</tok></cons></cons></cons> <cons cat="VP"><tok cat="JJ">located</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">positions</tok> <tok cat="CD">-102</tok></cons> <tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="CD">-73</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBP">have</tok> <tok cat="RB">not</tok> <cons cat="ADVP"><tok cat="RB">previously</tok></cons> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">described</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">regulators</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-5</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1035989510@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">BR3</tok> <tok cat="NN">sequence</tok></cons> <cons cat="VP"><tok cat="VBZ">contains</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="JJ">negative</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">element</tok></cons> <cons cat="VP"><tok cat="JJ">located</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">positions</tok> <tok cat="CD">-90</tok></cons> <tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="CD">-79</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">hIL-5</tok> <tok cat="NN">promoter</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i10"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i10" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">binds</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Oct1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">octamer-like</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">YY1</tok> <tok cat="JJ">nuclear</tok> <tok cat="NNS">factors</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1035989511@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Substitution</tok> <tok cat="NNS">mutations</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i11"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">abolished</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">proteins</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">BR3</tok> <tok cat="NN">sequence</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBD">increased</tok> <cons cat="NP"><tok cat="NN">hIL-5</tok> <tok cat="NN">promoter</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="VBN">activated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1035989512@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">CONCLUSION</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i12" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Oct1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">YY1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">octamer-like</tok> <tok cat="NNS">factors</tok></cons></cons> <cons cat="VP"><tok cat="VBG">binding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="CD">-90/-79</tok> <tok cat="NN">sequence</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">proximal</tok> <tok cat="NN">IL-5</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">suppression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-5</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1036415701@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Direct</tok> <tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">hematopoietic</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">PU.1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons></cons></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">functional</tok> <tok cat="NN">antagonism</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1036415702@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Malignant</tok> <tok cat="NN">transformation</tok></cons> <cons cat="ADVP"><tok cat="RB">usually</tok></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><tok cat="JJ">terminal</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">precise</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons></cons></cons><cons cat="VP"><tok cat="VBP">are</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">understood</tok><cons cat="NP" ref="i1" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1036415703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PU.1</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">hematopoietic-specific</tok> <tok cat="NN">Ets</tok> <tok cat="NN">family</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" id="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">development</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">some</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">lymphoid</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">myeloid</tok></cons></cons> <tok cat="NNS">lineages</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1036415704@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PU.1</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VB">act</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">oncoprotein</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">precursors</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">proviral</tok> <tok cat="NN">insertion</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">transgenesis</tok></cons> <cons cat="VP"><tok cat="VBZ">causes</tok> <cons cat="NP"><tok cat="NNS">erythroleukemias</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">mice</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1036415705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Restoration</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">terminal</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">mouse</tok> <tok cat="NN">erythroleukemia</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MEL</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">requires</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">decline</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">level</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PU.1</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">indicating</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PU.1</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">block</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1036415706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">investigate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">mechanism</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i4"><tok cat="IN">by</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PU.1</tok></cons> <cons cat="VP"><tok cat="VBZ">interferes</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">differentiation</tok></cons></cons><cons cat="PP" ref="i4" null="T"></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1036415707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">find</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PU.1</tok></cons> <cons cat="VP"><tok cat="VBZ">interacts</tok> <cons cat="ADVP"><tok cat="RB">directly</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">GATA-1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">zinc</tok> <tok cat="NN">finger</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1036415708@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Interaction</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">PU.1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">requires</tok> <cons cat="NP"><tok cat="JJ">intact</tok> <tok cat="JJ">DNA-binding</tok> <tok cat="NNS">domains</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">both</tok> <tok cat="NNS">proteins</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1036415709@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PU.1</tok></cons> <cons cat="VP"><tok cat="VBZ">represses</tok> <cons cat="NP"><tok cat="JJ">GATA-1-mediated</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activation</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@6@@oe@16-12-2010 1036415710@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i5" role="SBJ"><cons cat="NP" syn="COOD"><tok cat="CC">Both</tok> <tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NN">binding</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">transactivation</tok> <tok cat="NNS">domains</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PU.1</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">repression</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="DT">both</tok> <tok cat="NNS">domains</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">needed</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">block</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">terminal</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">MEL</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1036415711@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><tok cat="JJ">ectopic</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">PU.1</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">Xenopus</tok> <tok cat="NNS">embryos</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">sufficient</tok> <cons cat="S"><cons cat="NP" ref="i8" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">block</tok> <cons cat="NP"><tok cat="NN">erythropoiesis</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NN">development</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1036415712@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">introduction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">exogenous</tok> <tok cat="NN">GATA-1</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">MEL</tok> <tok cat="NNS">cells</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Xenopus</tok> <tok cat="NNS">embryos</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">explants</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">relieves</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">block</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="VP"><tok cat="VBN">imposed</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">PU.1</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1036415713@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">stoichiometry</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="RB">directly</tok> <tok cat="VBG">interacting</tok></cons> <tok cat="CC">but</tok> <cons cat="ADJP"><tok cat="VBG">opposing</tok></cons></cons> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">crucial</tok> <tok cat="NN">determinant</tok></cons> <cons cat="VP"><tok cat="VBG">governing</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">processes</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NN">differentiation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">malignant</tok> <tok cat="NN">transformation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1036419101@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="NN">Potent</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">stable</tok></cons></cons> <tok cat="NN">attenuation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">live-HIV-1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gain</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">proteolysis-resistant</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IkappaB-alphaS32/36A</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">implications</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">vaccine</tok> <tok cat="NN">development</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1036419102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Live-attenuated</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">immunodeficiency</tok> <tok cat="NNS">viruses</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">HIVs</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="NNS">candidates</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="VBN">Acquired</tok> <tok cat="NN">Immunodeficiency</tok> <tok cat="NN">Syndrome</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">AIDS</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">vaccine</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1036419103@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="VBN">Based</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">simian</tok> <tok cat="NN">immunodeficiency</tok> <tok cat="NN">virus</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">SIV</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">model</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">AIDS</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="NN">loss-of-function</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="PP"><tok cat="FW">e.g.</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">deletion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">accessory</tok> <tok cat="NNS">genes</tok></cons> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP"><tok cat="NN">nef</tok></cons></cons></cons></cons></cons></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">forwarded</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">primary</tok> <tok cat="NN">approach</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">creating</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">enfeebled</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="ADJP"><tok cat="JJ">replication-competent</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="NN">HIV-1/SIV</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1036419104@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Regrettably</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="JJ">recent</tok> <tok cat="NN">evidence</tok></cons> <cons cat="VP"><tok cat="VBZ">suggests</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">loss-of-function</tok></cons> <cons cat="ADJP"><tok cat="RB">alone</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="ADJP"><tok cat="RB">always</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">sufficient</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">prevent</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">emergence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">virulent</tok> <tok cat="NNS">mutants</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1036419105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">New</tok> <tok cat="NNS">strategies</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">attenuate</tok> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">mechanisms</tok></cons> <cons cat="ADJP"><tok cat="JJ">distinct</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">loss-of-function</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">needed</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">enhancing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">safety</tok> <tok cat="NN">phenotype</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NN">genome</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1036419106@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">propose</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gain-of-function</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1" null="ZERO"></cons><cons cat="S"><cons cat="NP" ref="i1" id="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">simultaneously</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">loss-of-function</tok></cons></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="NN">approach</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">attenuating</tok> <cons cat="NP"><tok cat="NN">HIV-1</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1036419107@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">constructed</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">HIV-1</tok> <tok cat="NN">genome</tok></cons> <cons cat="VP"><tok cat="VBG">carrying</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cDNA</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <cons cat="NP"><tok cat="JJ">proteolysis-resistant</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">factor-kappaB</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IkappaB-alphaS32/36A</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nef</tok> <tok cat="NN">region</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1036419108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="NN">HIV-1</tok></cons> <cons cat="VP"><tok cat="VBG">expressing</tok> <cons cat="NP"><tok cat="NN">IkappaB-alphaS32/36A</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">down-regulates</tok> <cons cat="NP"><tok cat="JJ">viral</tok> <tok cat="NN">expression</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">highly</tok></cons> <cons cat="VP"><tok cat="VBN">attenuated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">Jurkat</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="JJ">mononuclear</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1036419109@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">provide</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">formal</tok> <tok cat="NN">proof</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">phenotypic</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="NN">attenuating</tok></cons></cons> <tok cat="NNS">characteristics</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IkappaB-alphaS32/36A</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">permit</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">stable</tok> <tok cat="NN">maintenance</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">live</tok></cons><tok cat="COMMA">,</tok> <cons cat="ADJP"><tok cat="VBG">replicating</tok></cons></cons> <tok cat="NN">HIV-1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">despite</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">180</tok> <tok cat="NNS">days</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">forced</tok> <cons cat="ADJP"><tok cat="FW">ex</tok> <tok cat="FW">vivo</tok></cons> <tok cat="NN">passaging</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">tissue</tok> <tok cat="NN">culture</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1036419110@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">As</tok> <cons cat="FRAG"><cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="JJ">open-reading</tok> <tok cat="NNS">frames</tok></cons> <cons cat="VP"><tok cat="JJ">embedded</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="NN">HIV/SIV</tok> <tok cat="NN">genome</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">degree</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">stability</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">unprecedented</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1036419111@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Thus</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">IkappaB-alphaS32/36A</tok></cons> <cons cat="VP"><tok cat="VBZ">offers</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">proof-of-principle</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i9" role="SBJ"><cons cat="ADJP"><tok cat="RB">artifactually</tok> <tok cat="VBN">gained</tok></cons> <tok cat="NNS">functions</tok></cons><cons cat="PRN"><tok cat="COMMA">,</tok> <cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i8"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" ref="i9" id="i12" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">attenuate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">replication</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">live</tok> <tok cat="NN">HIV-1</tok></cons></cons></cons></cons></cons></cons><cons cat="ADVP" ref="i8" null="T"></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">stable</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1036419112@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">illustrate</tok> <cons cat="NP"><tok cat="NN">gain-of-function</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">feasible</tok> <tok cat="NN">strategy</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">developing</tok> <cons cat="NP"><cons cat="NP" id="i10"><tok cat="JJR">safer</tok> <tok cat="JJ">live-attenuated</tok> <tok cat="NNS">HIVs</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i13" null="ZERO"></cons><cons cat="S"><cons cat="NP" ref="i13" id="i14" role="SBJ" null="T"></cons><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">tested</tok> <cons cat="NP" ref="i14" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">candidates</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">AIDS</tok> <tok cat="NN">vaccine</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1036419301@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP" role="SBJ"><tok cat="JJ">Oxidative</tok> <tok cat="NN">stress</tok></cons> <cons cat="VP"><tok cat="VBZ">triggers</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT3</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1036419302@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Oxidizing</tok> <tok cat="NNS">agents</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="JJ">powerful</tok> <tok cat="NNS">activators</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">factors</tok></cons> <cons cat="ADJP"><tok cat="JJ">responsible</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cytokine-encoding</tok> <tok cat="NNS">genes</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">tissue</tok> <tok cat="NN">injury</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1036419303@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">evidence</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">STAT3</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WPP">whose</tok> <tok cat="NN">activity</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" id="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">modulated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">H2O2</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">lymphocytes</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHPP" id="i3"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="JJ">endogenous</tok> <tok cat="NN">catalase</tok></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="ADVP"><tok cat="RB">previously</tok></cons> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">inhibited</tok><cons cat="NP" ref="i4" null="NONE"></cons></cons></cons><cons cat="PP" ref="i3" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1036419304@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">H2O2-induced</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT3</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">form</tok> <cons cat="NP"><tok cat="JJ">sequence-specific</tok> <tok cat="JJ">DNA-bound</tok> <tok cat="NNS">complexes</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">evidenced</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">immunoblotting</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NNS">fractions</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">electrophoretic</tok> <tok cat="NN">mobility</tok> <tok cat="NN">shift</tok> <tok cat="NNS">assays</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="NN">vanadate</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="ADVP"><tok cat="RB">strongly</tok></cons> <cons cat="VP"><tok cat="VB">synergize</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">H2O2</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1036419305@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="JJ">anti-STAT3</tok> <tok cat="NNS">antibodies</tok></cons> <cons cat="ADVP"><tok cat="RB">specifically</tok></cons> <cons cat="VP"><tok cat="VBD">precipitated</tok> <cons cat="NP"><cons cat="NP" id="i9"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">protein</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="CD">92</tok> <tok cat="NN">kDa</tok></cons></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i8"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i8" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">becomes</tok> <cons cat="ADJP" role="PRD"><tok cat="VBN">phosphorylated</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">tyrosine</tok></cons></cons> <cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">lymphocyte</tok> <tok cat="NN">treatment</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">H2O2</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1036419306@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Phenylarsine</tok> <tok cat="NN">oxide</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">phosphatase</tok> <tok cat="NN">inhibitor</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">genistein</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">kinase</tok> <tok cat="NN">inhibitor</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">cooperated</tok> <cons cat="NP" ref="i11" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">cancelled</tok><cons cat="NP" ref="i11" null="RNR"></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">respectively</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i11"><tok cat="DT">the</tok> <tok cat="JJ">H2O2-promoted</tok> <tok cat="NN">STAT3</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1036419307@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i12" role="SBJ"><tok cat="NN">Evidence</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">presented</tok><cons cat="NP" ref="i12" null="NONE"></cons><cons cat="PRN"><tok cat="COMMA">,</tok> <cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="JJ">Fe2+/Cu2+</tok> <tok cat="NNS">ions</tok></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="SBAR"><tok cat="IN">that.</tok><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">OH</tok></cons> <cons cat="VP"><tok cat="VBN">generated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">H2O2</tok></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="NN">Fenton</tok> <tok cat="NNS">reactions</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">could</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">candidate</tok> <tok cat="NN">oxygen</tok> <tok cat="JJ">reactive</tok> <tok cat="NNS">species</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="ADVP"><tok cat="RB">directly</tok></cons> <cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><tok cat="NN">STAT3</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1036419308@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Present</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i13" role="SBJ"><cons cat="NP"><tok cat="NN">H2O2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">vanadate</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP"><tok cat="JJ">likely</tok> <cons cat="S" role="PRD"><cons cat="NP" ref="i13" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">inhibit</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">intracellular</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">phosphatase</tok><cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">s</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">leading</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="VBN">enhanced</tok> <tok cat="NN">STAT3</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">hence</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">translocation</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nucleus</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1036419309@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i14" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT3</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">modulated</tok> <cons cat="NP" ref="i14" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="VBG">oxidizing</tok> <tok cat="NNS">agents</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">provide</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">framework</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">understand</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">oxidative</tok> <tok cat="NN">stress</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">JAK-STAT</tok> <tok cat="NN">signaling</tok> <tok cat="NN">pathway</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1036426001@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Human</tok> <tok cat="JJ">alveolar</tok> <tok cat="NNS">macrophages</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">markedly</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">deficient</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">REF-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1036426002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">Although</tok> <cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="JJ">many</tok> <tok cat="NNS">functions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">alveolar</tok> <tok cat="NNS">macrophages</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">altered</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">precursor</tok> <tok cat="NN">cell</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">blood</tok> <tok cat="NN">monocyte</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">monocyte</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">reason</tok><cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">s</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="JJ">functional</tok> <tok cat="NNS">changes</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">determined</tok><cons cat="NP" ref="i2" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1036426003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">recently</tok></cons> <cons cat="VP"><tok cat="VBD">reported</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">human</tok> <tok cat="JJ">alveolar</tok> <tok cat="NNS">macrophages</tok></cons> <cons cat="VP"><tok cat="VBP">do</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">express</tok> <cons cat="NP"><tok cat="NN">AP-1</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="NNP">Monick</tok><tok cat="COMMA">,</tok> <tok cat="NNP">M.</tok> <tok cat="NNP">M.</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">Carter</tok><tok cat="COMMA">,</tok> <tok cat="NNP">A.</tok> <tok cat="NNP">B.</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">Gudmundsson</tok><tok cat="COMMA">,</tok> <tok cat="NNP">G.</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NNP">Geist</tok><tok cat="COMMA">,</tok> <tok cat="NNP">L.</tok> <tok cat="NNP">J.</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNP">Hunninghake</tok><tok cat="COMMA">,</tok> <tok cat="NNP">G.</tok> <tok cat="NNP">W.</tok></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">1998</tok></cons><tok cat="RRB">)</tok></cons> <cons cat="NP"><tok cat="NNP">Am.</tok> <tok cat="NNP">J.</tok> <tok cat="NNP">Physiol.</tok> <tok cat="CD">275</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">L389-L397</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@50@@oe@16-12-2010 1036426004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">determine</tok> <cons cat="SBAR"><cons cat="WHADVP" id="i3"><tok cat="WRB">why</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">alveolar</tok> <tok cat="NNS">macrophages</tok></cons> <cons cat="VP"><tok cat="VBP">do</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">express</tok> <cons cat="NP"><tok cat="NN">AP-1</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons><cons cat="ADVP" ref="i3" null="T"></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="ADVP"><tok cat="RB">first</tok></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="EX">there</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">decrease</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">FOS</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">JUN</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><cons cat="NP" id="i4"><tok cat="NNS">proteins</tok></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">make</tok> <tok cat="RP">up</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">AP-1</tok> <tok cat="NN">complex</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1036426005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="EX">There</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">significant</tok> <tok cat="NN">difference</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">amounts</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">protein</tok><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">REF-1</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" id="i7" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">regulates</tok> <cons cat="NP"><tok cat="NN">AP-1</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">altering</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">redox</tok> <tok cat="NN">status</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">FOS</tok> <tok cat="CC">and</tok> <tok cat="NN">JUN</tok> <tok cat="NNS">proteins</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">alveolar</tok> <tok cat="NNS">macrophages</tok></cons> <cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@42@@oe@16-12-2010 1036426006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">macrophage-like</tok> <tok cat="NN">cell</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">resulted</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">decreased</tok> <tok cat="NNS">amounts</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">REF-1</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1036426007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Finally</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">REF-1</tok></cons></cons></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="VBN">activated</tok> <tok cat="NNS">monocytes</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">alveolar</tok> <tok cat="NN">macrophage</tok> <tok cat="JJ">nuclear</tok> <tok cat="NNS">proteins</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">resulted</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">marked</tok> <tok cat="NN">increase</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">AP-1</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1036426008@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">studies</tok></cons> <cons cat="ADVP"><tok cat="RB">strongly</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">process</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="JJ">alveolar</tok> <tok cat="NNS">macrophages</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">loss</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">REF-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">AP-1</tok></cons></cons> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1036426009@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">observation</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">explain</tok><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">part</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">some</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">functional</tok> <tok cat="NNS">differences</tok></cons> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">alveolar</tok> <tok cat="NNS">macrophages</tok></cons> <cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1036660001@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Monocyte</tok> <tok cat="NN">adhesion</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">spreading</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">dependent</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">Rho-regulated</tok> <tok cat="NN">receptor</tok> <tok cat="NN">clustering</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1036660002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="NN">GTPase</tok></cons> <cons cat="NP"><tok cat="NN">Rho</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">mediate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">assembly</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">integrin-containing</tok> <tok cat="JJ">focal</tok> <tok cat="NNS">adhesions</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">actin</tok> <tok cat="NN">stress</tok> <tok cat="NNS">fibers</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1036660003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">investigate</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Rho</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">regulating</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">distribution</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">monocyte-binding</tok> <tok cat="NNS">receptors</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">E-selectin</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">ICAM-1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">VCAM-1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1036660004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Rho</tok> <tok cat="NN">activity</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">C3</tok> <tok cat="NN">transferase</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">N19RhoA</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dominant</tok> <tok cat="JJ">negative</tok> <tok cat="NN">RhoA</tok> <tok cat="NN">mutant</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">reduced</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">adhesion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="VBN">activated</tok> <tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">spreading</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1036660005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="JJ">Similar</tok> <tok cat="NNS">effects</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">pretreatment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">cytochalasin</tok> <tok cat="NN">D</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1036660006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="JJ">dominant</tok> <tok cat="JJ">negative</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Rac</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Cdc42</tok> <cons cat="NP" ref="i5" null="RNR"></cons></cons><cons cat="NP" id="i5"><tok cat="NNS">proteins</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">monocyte</tok> <tok cat="NN">adhesion</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">spreading</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1036660007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">C3</tok> <tok cat="NN">transferase</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cytochalasin</tok> <tok cat="NN">D</tok></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">alter</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">monocyte-binding</tok> <tok cat="NNS">receptors</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBD">did</tok> <cons cat="VP"><tok cat="VB">inhibit</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">clustering</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">E-selectin</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">ICAM-1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">VCAM-1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cell</tok> <tok cat="NN">surface</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><cons cat="NP"><tok cat="NN">monocyte</tok> <tok cat="NN">adhesion</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">cross-linking</tok> <tok cat="NNS">antibodies</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1036660008@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Similarly</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">N19RhoA</tok></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><tok cat="NN">receptor</tok> <tok cat="NN">clustering</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@7@@oe@16-12-2010 1036660009@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">Monocyte</tok> <tok cat="NN">adhesion</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">receptor</tok> <tok cat="NN">cross-linking</tok></cons></cons> <cons cat="VP"><tok cat="JJ">induced</tok> <cons cat="NP"><tok cat="NN">stress</tok> <tok cat="NN">fiber</tok> <tok cat="NN">assembly</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">inhibitors</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">myosin</tok> <tok cat="JJ">light</tok> <tok cat="NN">chain</tok> <tok cat="NN">kinase</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">prevented</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">response</tok></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP"><tok cat="NN">receptor</tok> <tok cat="NN">clustering</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1036660010@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Finally</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">receptor</tok> <tok cat="NNS">clusters</tok></cons> <cons cat="VP"><tok cat="VBD">colocalized</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">ezrin/moesin/radixin</tok> <tok cat="NNS">proteins</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@9@@oe@16-12-2010 1036660011@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="NN">Rho</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">assembly</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">stable</tok> <tok cat="NNS">adhesions</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">clustering</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">monocyte-binding</tok> <tok cat="NNS">receptors</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">association</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">actin</tok> <tok cat="NN">cytoskeleton</tok></cons><tok cat="COMMA">,</tok> <cons cat="ADJP"><tok cat="JJ">independent</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">stress</tok> <tok cat="NN">fiber</tok> <tok cat="NN">formation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1036769801@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">Binding</tok> <tok cat="NNS">characteristics</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">glucocorticoid</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">multiple</tok> <tok cat="NN">sclerosis</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1036769802@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">Although</tok> <cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">exact</tok> <tok cat="NN">etiology</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">multiple</tok> <tok cat="NN">sclerosis</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MS</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">remains</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">unresolved</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><tok cat="JJ">immune</tok> <tok cat="NNS">reactions</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">believed</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP" role="PRD"><tok cat="DT">the</tok> <tok cat="JJ">central</tok> <tok cat="JJ">pathogenic</tok> <tok cat="NNS">mechanisms</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1036769803@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">Endogenous</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">therapeutic</tok></cons></cons> <tok cat="NN">steroid</tok> <tok cat="NNS">hormones</tok></cons> <cons cat="VP"><tok cat="VBP">affect</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">immune</tok> <tok cat="NN">system</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="JJ">inflammatory</tok> <tok cat="NNS">diseases</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">hypothalamic-pituitary-adrenal</tok> <tok cat="NN">axis</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">providing</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">evidence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">immune-endocrine</tok> <tok cat="NN">interplay</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1036769804@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Function</tok> <tok cat="NNS">tests</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">MS</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">revealed</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">dysregulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">hypothalamic-pituitary-adrenal</tok> <tok cat="NN">system</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">substantial</tok> <tok cat="NN">proportion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">patients</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1036769805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">characterized</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">glucocorticoid</tok> <tok cat="NN">receptor</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">GR</tok></cons><tok cat="RRB">)</tok></cons> <tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">39</tok> <tok cat="NN">MS</tok> <tok cat="NNS">patients</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="CD">14</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="NN">age-</tok> <cons cat="ADJP" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">sex-matched</tok></cons></cons> <tok cat="NNS">controls</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">respect</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">dissociation</tok> <tok cat="NN">constant</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">binding</tok> <tok cat="NN">capacity</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">whole-cell</tok> <tok cat="NN">binding</tok> <tok cat="NN">assay</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">[3H]dexamethasone</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ligand</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@42@@oe@16-12-2010 1036769806@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">GR</tok> <tok cat="NN">binding</tok> <tok cat="NNS">parameters</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">differ</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="NN">Kd</tok> <tok cat="CD">8.98</tok> <tok cat="CC">+/-</tok> <tok cat="CD">1.07</tok> <tok cat="NN">nM</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">Bmax</tok> <tok cat="CD">183</tok> <tok cat="CC">+/-</tok> <tok cat="CD">29.8</tok> <tok cat="NN">fmol/mg</tok></cons></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">controls</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="NN">Kd</tok> <tok cat="CD">9.36</tok> <tok cat="CC">+/-</tok> <tok cat="CD">1.17</tok> <tok cat="NN">nM</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">Bmax</tok> <tok cat="CD">158</tok> <tok cat="CC">+/-</tok> <tok cat="CD">16</tok> <tok cat="NN">fmol/mg</tok></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1036769807@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">No</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">age</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">sex</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">course</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">duration</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">severity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">disease</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">prior</tok> <tok cat="NN">steroid</tok> <tok cat="NNS">treatments</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">detected</tok><cons cat="NP" ref="i4" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1036769808@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NN">GR</tok> <tok cat="NN">binding</tok> <tok cat="NNS">parameters</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">analyzed</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">relation</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">results</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">combined</tok> <tok cat="JJ">dexamethasone-CRH</tok> <tok cat="NN">test</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">reflects</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">corticosteroid</tok> <tok cat="NN">receptor</tok> <tok cat="NN">function</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">hypothalamus</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">30</tok> <tok cat="NNS">patients</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="CD">9</tok> <tok cat="NNS">controls</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1036769809@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">While</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NNS">controls</tok></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">moderate</tok> <tok cat="NN">correlation</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok> <tok cat="NN">affinity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">GR</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">regulatory</tok> <tok cat="NN">function</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">hypothalamic</tok> <tok cat="NN">level</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NNS">patients</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok><cons cat="VP" null="QSTN"></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1036769810@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">physiological</tok> <tok cat="NN">relationship</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">binding</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">function</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">glucocorticoid</tok> <tok cat="NN">receptor</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">disturbed</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">MS</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1036789701@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">CBP/p300</tok></cons> <cons cat="VP"><tok cat="VBZ">integrates</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">Raf/Rac-signaling</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-ATc</tok></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1036789702@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">NF-ATc</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">an</tok> <cons cat="ADJP"><tok cat="RB">inducibly</tok> <tok cat="VBN">expressed</tok></cons> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">controls</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">cardiomyocytes</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1036789703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="ADVP"><tok cat="RB">here</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NNS">co-activators</tok></cons> <cons cat="NP"><tok cat="NN">CBP/p300</tok></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">bind</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">control</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">inducible</tok> <tok cat="JJ">N-terminal</tok> <tok cat="NN">transactivation</tok> <tok cat="NN">domain</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NF-ATc</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">TAD-A</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1036789704@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><cons cat="ADJP" role="PRD"><tok cat="JJ">Similar</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">N</tok> <tok cat="JJ">terminal</tok> <tok cat="NN">transactivation</tok> <tok cat="NN">domain</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">c-Jun</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">TAD-A</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">inducibly</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="VBN">phosphorylated</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">this</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">dispensable</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">CBP/p300</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1036789705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Constitutive</tok> <cons cat="NP"><tok cat="JJ">active</tok> <tok cat="NNS">versions</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">c-Raf</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Rac</tok></cons></cons></cons></cons> <cons cat="ADVP"><tok cat="RB">synergistically</tok></cons> <cons cat="VP"><tok cat="VBP">enhance</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">CBP/p300-mediated</tok> <tok cat="NN">increase</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TAD-A</tok> <tok cat="NN">activity</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">indicating</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">important</tok> <tok cat="NN">role</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2" null="ZERO"></cons><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">CBP/p300</tok></cons> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP" ref="i2" null="T"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">integration</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok> <tok cat="NNS">signals</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1036789706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">Since</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">mutation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CBP</tok> <tok cat="VBG">abolishing</tok> <tok cat="NN">HAT</tok> <tok cat="NN">activity</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">almost</tok></cons> <cons cat="ADJP" role="PRD"><cons cat="ADJP"><tok cat="RB">as</tok> <tok cat="JJ">active</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">wild-type</tok> <tok cat="NN">CBP</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="NNS">functions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">CBP/p300</tok></cons> <cons cat="CONJP"><tok cat="JJ">other</tok> <tok cat="IN">than</tok></cons> <cons cat="NP"><tok cat="NN">histone</tok> <tok cat="NN">acetylation</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">appear</tok> <cons cat="S" role="PRD"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">control</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">NF-AT-dependent</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1036925501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="NN">polymorphism</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">affects</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">OCT-1</tok> <tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">TNF</tok> <tok cat="NN">promoter</tok> <tok cat="NN">region</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">severe</tok> <tok cat="NN">malaria</tok></cons></cons> <cons cat="PRN"><tok cat="LRB">[</tok><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VB">see</tok> <cons cat="NP"><tok cat="NNS">comments</tok></cons></cons></cons><tok cat="RRB">]</tok></cons></cons></cons></cons>@@@@1@20@@oe@16-12-2010 1036925502@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="JJ">Genetic</tok> <tok cat="NN">variation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NN">promoter</tok> <tok cat="NNS">regions</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">postulated</tok> <cons cat="NP" ref="i3" id="i9" null="NONE"></cons><cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">influence</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">susceptibility</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">infection</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">molecular</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i5"><tok cat="IN">by</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">such</tok> <tok cat="NNS">polymorphisms</tok></cons> <cons cat="VP"><tok cat="MD">might</tok> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP" ref="i5" null="T"></cons></cons></cons></cons></cons></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="JJ">unknown</tok><cons cat="NP" ref="i4" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1036925503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Through</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">systematic</tok> <tok cat="NN">DNA</tok> <tok cat="NN">footprinting</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">TNF</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="VBG">encoding</tok> <tok cat="NN">tumour</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">TNF</tok></cons></cons><tok cat="RRB">)</tok></cons> <tok cat="NN">promoter</tok> <tok cat="NN">region</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">identified</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">single</tok> <tok cat="NN">nucleotide</tok> <tok cat="NN">polymorphism</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">SNP</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="T"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">causes</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="JJ">helix-turn-helix</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">OCT-1</tok></cons> <cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">bind</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="NN">region</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">complex</tok> <tok cat="JJ">protein-DNA</tok> <tok cat="NNS">interactions</tok></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">alters</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@53@@oe@16-12-2010 1036925504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">OCT-1-binding</tok> <tok cat="NN">genotype</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="QP"><tok cat="RB">approximately</tok> <tok cat="CD">5</tok></cons><tok cat="NN">%</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">Africans</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><cons cat="ADJP"><tok cat="RB">fourfold</tok> <tok cat="VBN">increased</tok></cons> <tok cat="NN">susceptibility</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">cerebral</tok> <tok cat="NN">malaria</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">large</tok> <tok cat="JJ">case-control</tok> <tok cat="NNS">studies</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">West</tok> <tok cat="JJ">African</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">East</tok> <tok cat="JJ">African</tok></cons></cons> <tok cat="NNS">populations</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">correction</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="JJ">known</tok> <tok cat="NN">TNF</tok> <tok cat="NNS">polymorphisms</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="VBN">linked</tok> <tok cat="NN">HLA</tok> <tok cat="NNS">alleles</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@45@@oe@16-12-2010 1036941901@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Association</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">interleukin-4</tok> <tok cat="NN">receptor</tok> <tok cat="NN">alpha</tok> <tok cat="NN">chain</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">p47phox</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">activator</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">phagocyte</tok> <tok cat="NN">NADPH</tok> <tok cat="NN">oxidase</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1036941902@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Interleukin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="CD">-4</tok></cons> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">important</tok> <tok cat="NN">role</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IgE</tok> <tok cat="NN">synthesis</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Th2</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1036941903@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="NN">IL-4</tok></cons> <cons cat="VP"><tok cat="VBZ">conducts</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">biological</tok> <tok cat="NNS">activities</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">binding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-4</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-4R</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">surface</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">target</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1036941904@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NN">IL-4R</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">thought</tok> <cons cat="S"><cons cat="NP" ref="i2" id="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">composed</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-4R</tok> <tok cat="NN">alpha</tok> <tok cat="NN">chain</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-4R</tok> <tok cat="NN">alpha</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP" syn="COOD"><tok cat="CC">either</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-2R</tok> <tok cat="NN">gamma</tok> <tok cat="NN">chain</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IL-13R</tok> <tok cat="NN">alpha</tok> <tok cat="NN">chain</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1036941905@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="ADVP"><tok cat="RB">previously</tok></cons> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">membrane-proximal</tok> <tok cat="NN">portion</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cytoplasmic</tok> <tok cat="NN">domain</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">IL-4R</tok> <tok cat="NN">alpha</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">hIL-4R</tok> <tok cat="NN">alpha</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">critical</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">proliferation</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">generation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">germline</tok> <tok cat="NN">epsilon</tok> <tok cat="NN">transcript</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT6</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBN">based</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">analyses</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">truncated</tok> <tok cat="NN">hIL-4R</tok> <tok cat="NNS">alphas</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@45@@oe@16-12-2010 1036941906@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">p47phox</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">activator</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">phagocyte</tok> <tok cat="NN">NADPH</tok> <tok cat="NN">oxidase</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">binds</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">portion</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">two-hybrid</tok> <tok cat="NN">system</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1036941907@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">observed</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">association</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">p47phox</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">hIL-4R</tok> <tok cat="NN">alpha</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">derived</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">normal</tok> <tok cat="NN">donor</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1036941908@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="NN">p47phox</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">signal</tok> <tok cat="NN">transduction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-4</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1036941909@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" id="i5" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT6</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">CD23</tok> <tok cat="NN">expression</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IgE</tok> <tok cat="NN">synthesis</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">IL-4</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">affected</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">p47phox-deficient</tok> <tok cat="NNS">patients</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">raises</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">possibility</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">p47phox</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">important</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">other</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">activities</tok></cons></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1036968101@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="NN">Aiolos</tok></cons> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">controls</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">death</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">regulating</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Bcl-2</tok> <tok cat="NN">expression</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">cellular</tok> <tok cat="NN">localization</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1036968102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">searched</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">proteins</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">interact</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Ras</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="JJ">-2-stimulated</tok></cons> <tok cat="CC">or</tok> <cons cat="ADJP"><tok cat="JJ">IL-2-deprived</tok></cons></cons> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="NP"><tok cat="NN">Aiolos</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">interacts</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Ras</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1036968103@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">Ras-Aiolos</tok> <tok cat="NN">interaction</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">confirmed</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="ADVP" syn="COOD"><cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vivo</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">co-immunoprecipitation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1036968104@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Indirect</tok> <tok cat="NN">immunofluorescence</tok></cons> <cons cat="VP"><tok cat="VBZ">shows</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-2</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">controls</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cellular</tok> <tok cat="NN">distribution</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Aiolos</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">dissociation</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">Ras</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1036968105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBD">identified</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">functional</tok> <tok cat="JJ">Aiolos-binding</tok> <tok cat="NNS">sites</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Bcl-2</tok> <tok cat="NN">promoter</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" id="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">able</tok> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">luciferase</tok> <tok cat="NN">reporter</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1036968106@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Mutation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">Aiolos-binding</tok> <tok cat="NNS">sites</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Bcl-2</tok> <tok cat="NN">promoter</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">transactivation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">reporter</tok> <tok cat="NN">gene</tok> <tok cat="NN">luciferase</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">suggesting</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">direct</tok> <tok cat="NN">control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Bcl-2</tok> <tok cat="NN">expression</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">Aiolos</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1036968107@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Co-transfection</tok> <tok cat="NNS">experiments</tok></cons> <cons cat="VP"><tok cat="VBP">confirm</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Aiolos</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><tok cat="NN">Bcl-2</tok> <tok cat="NN">expression</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">prevents</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">apoptosis</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">IL-2-deprived</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1036968108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">propose</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">model</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Bcl-2</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><tok cat="NN">Aiolos</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1037037201@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">rheumatoid</tok> <tok cat="NN">arthritis</tok></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">correlation</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">inflammation</tok></cons><tok cat="COMMA">,</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="NN">disease</tok> <tok cat="NN">specificity</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1037037202@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="JJ">Rheumatoid</tok> <tok cat="NN">arthritis</tok> <tok cat="JJ">synovial</tok> <tok cat="NN">tissue</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBN">examined</tok> <cons cat="NP" ref="i1" null="NONE"></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBN">compared</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">osteoarthritis</tok> <tok cat="NN">tissue</tok></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok> <tok cat="LRB">(</tok><tok cat="NN">NF-IL-6</tok><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1037037203@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP" syn="COOD"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="NN">region</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">lining</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">sublining</tok></cons></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">type</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">subcellular</tok> <tok cat="NN">distribution</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">cytoplasmic</tok></cons> <tok cat="CC">or</tok> <cons cat="ADJP"><tok cat="JJ">nuclear</tok></cons></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">characterized</tok><cons cat="NP" ref="i2" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1037037204@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" id="i4" role="SBJ"><cons cat="NP"><tok cat="JJ">Rheumatoid</tok> <tok cat="NN">arthritis</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">synovial</tok> <tok cat="NN">fluid</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">blood</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">examined</tok><cons cat="NP" ref="i4" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1037037205@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">synovial</tok> <tok cat="NN">lining</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">sublining</tok> <tok cat="NNS">cells</tok> <tok cat="IN">of</tok> <tok cat="JJ">synovial</tok> <tok cat="NN">tissue</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="JJ">rheumatoid</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">osteoarthritis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1037037206@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="JJ">significant</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">P</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="JJR"><</tok> <cons cat="NP"><tok cat="CD">0.001</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="JJR"><</tok> <cons cat="NP"><tok cat="CD">0.05</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">respectively</tok></cons></cons></cons><tok cat="RRB">)</tok></cons> <tok cat="NN">increase</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">percentage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">staining</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">seen</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">lining</tok> <tok cat="NN">layer</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">sublining</tok> <tok cat="NN">region</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">rheumatoid</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">osteoarthritis</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1037037207@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">both</tok> <tok cat="NNS">diseases</tok></cons></cons> <cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">strong</tok> <tok cat="NN">correlation</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">r</tok></cons> <cons cat="VP"><tok cat="JJ">=</tok> <cons cat="NP"><tok cat="CD">0.79</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">P</tok></cons> <cons cat="VP"><tok cat="JJR"><</tok> <cons cat="NP"><tok cat="CD">0.001</tok></cons></cons></cons></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">percentage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">synovial</tok> <tok cat="NN">lining</tok></cons></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i9"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">positive</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">lining</tok> <tok cat="NN">cell</tok> <tok cat="NN">depth</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1037037208@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Two-color</tok> <tok cat="NN">immunohistochemistry</tok></cons> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NNS">macrophages</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">fibroblast-like</tok> <tok cat="NNS">synoviocytes</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">positive</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1037037209@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i10" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">confirmed</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">immunohistochemistry</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Western</tok> <tok cat="NN">blot</tok> <tok cat="NN">analysis</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="VBN">isolated</tok> <tok cat="JJ">synovial</tok> <tok cat="NNS">fibroblasts</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1037037210@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i11" role="SBJ"><tok cat="JJ">Nuclear</tok> <tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">rheumatoid</tok> <tok cat="JJ">synovial</tok> <tok cat="NN">fluid</tok> <cons cat="NP"><tok cat="NNS">monocytes/macrophages</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">lymphocytes</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NNS">neutrophils</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1037037211@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Western</tok> <tok cat="NN">blot</tok> <tok cat="NN">analysis</tok></cons> <cons cat="VP"><tok cat="VBD">confirmed</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1037037212@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">intensity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok> <tok cat="NN">staining</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJR">greater</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">P</tok></cons> <cons cat="VP"><tok cat="JJR"><</tok> <cons cat="NP"><tok cat="CD">0.001</tok></cons></cons></cons><tok cat="RRB">)</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">synovial</tok> <tok cat="NN">fluid</tok> <tok cat="NNS">monocytes</tok></cons></cons> <cons cat="CONJP"><tok cat="IN">than</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">normal</tok></cons> <tok cat="CC">or</tok> <cons cat="ADJP"><tok cat="JJ">rheumatoid</tok></cons></cons> <tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1037037213@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">conclusion</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">enhanced</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">staining</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">synovial</tok> <tok cat="NN">lining</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">compared</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">sublining</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">suggesting</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">lining</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">positive</tok> <tok cat="NN">correlation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">lining</tok> <tok cat="NN">layer</tok> <tok cat="NN">depth</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">percentage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">cells</tok></cons> <cons cat="NP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">lining</tok></cons> <cons cat="ADJP"><tok cat="JJ">positive</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">potential</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">inflammation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@59@@oe@16-12-2010 1037037214@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">production</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">activity</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">C/EBP</tok> <tok cat="NN">beta</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">inhibit</tok> <cons cat="NP"><tok cat="JJ">inflammatory</tok> <tok cat="NN">mediator</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">synovial</tok> <tok cat="NNS">macrophages</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">fibroblasts</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">offers</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="NN">approach</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">therapeutic</tok> <tok cat="NN">intervention</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1037227101@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Novel</tok> <tok cat="NNS">therapies</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">inflammatory</tok> <tok cat="NN">bowel</tok> <tok cat="NN">disease</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@7@@oe@16-12-2010 1037227102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">Looking</tok> <cons cat="ADVP"><tok cat="RB">back</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">successes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">failures</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJR">newer</tok> <tok cat="NNS">approaches</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">treating</tok> <cons cat="NP"><tok cat="NN">IBD</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="PRP">it</tok></cons> <cons cat="S" ref="i1" null="EXP"></cons></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">tempting</tok><cons cat="PRN"><tok cat="COLON">--</tok><cons cat="SBAR"><tok cat="IN">although</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">still</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">difficult</tok></cons></cons></cons><tok cat="COLON">--</tok></cons><cons cat="S" id="i1"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">draw</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">conclusions</tok></cons> <cons cat="PP"><tok cat="IN">about</tok> <cons cat="NP"><tok cat="NN">pathogenesis</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1037227103@GENIA Treebank@formal@@1@S@<cons cat="UCP" syn="COOD"><cons cat="SBARQ"><cons cat="WHADVP" id="i3" adv="TMP"><tok cat="WRB">When</tok></cons> <cons cat="SQ"><cons cat="NP" role="SBJ"><tok cat="DT">a</tok> <tok cat="NN">therapy</tok></cons> <cons cat="VP"><tok cat="VBZ">proves</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">effective</tok></cons><cons cat="ADVP" ref="i3" null="T"></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SQ"><tok cat="VBP">do</tok> <cons cat="NP" role="SBJ"><tok cat="NNS">clinicians</tok></cons> <cons cat="ADVP"><tok cat="RB">truly</tok></cons> <cons cat="VP"><tok cat="VB">know</tok> <cons cat="SBAR"><cons cat="WHADVP" id="i4"><tok cat="WRB">how</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="VBZ">works</tok><cons cat="ADVP" ref="i4" null="T"></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">?</tok></cons>@@@@1@14@@oe@16-12-2010 1037227104@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><cons cat="ADVP"><tok cat="RB">Even</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">therapy</tok></cons> <cons cat="ADJP"><cons cat="ADJP"><tok cat="IN">as</tok> <tok cat="JJ">specific</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="JJ">anti-TNF</tok> <tok cat="NN">antibody</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">clear</tok></cons> <cons cat="SBAR"><tok cat="IN">if</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">benefit</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">attributable</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><tok cat="JJ">simple</tok> <cons cat="NP"><tok cat="NN">binding</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">clearance</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cell</tok> <tok cat="NN">surface</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">subsequent</tok> <tok cat="NN">deletion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">activated</tok> <tok cat="NN">macrophage</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1037227105@GENIA Treebank@formal@@1@S@<cons cat="SQ"><cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i6"><tok cat="WRB">When</tok></cons> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="DT">a</tok> <tok cat="NN">drug</tok></cons> <cons cat="VP"><tok cat="VBZ">appears</tok> <cons cat="S" role="PRD"><cons cat="NP" ref="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADJP" role="PRD"><cons cat="ADJP"><tok cat="RBR">less</tok> <tok cat="JJ">effective</tok></cons> <cons cat="SBAR"><tok cat="IN">than</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">preclinical</tok> <tok cat="NNS">models</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="MD">can</tok> <cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><tok cat="NNS">failures</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">effectiveness</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">delivery</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">dosing</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">differentiated</tok><cons cat="NP" ref="i8" null="NONE"></cons></cons></cons><tok cat="PERIOD">?</tok></cons>@@@@1@24@@oe@16-12-2010 1037227106@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">disappointing</tok> <tok cat="NNS">results</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">clinical</tok> <tok cat="NNS">trials</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons></cons></cons></cons><cons cat="PRN"><tok cat="COLON">--</tok><cons cat="ADVP"><tok cat="RB">so</tok></cons> <cons cat="ADVP"><tok cat="IN">at</tok> <tok cat="NNS">odds</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">prediction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">benefit</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">animal</tok> <tok cat="NNS">models</tok></cons></cons></cons></cons></cons></cons><tok cat="COLON">--</tok></cons></cons><cons cat="VP"><tok cat="VBP">bring</tok> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="NN">question</tok></cons></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">validity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">those</tok> <tok cat="NNS">models</tok></cons></cons></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">soundness</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">design</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">clinical</tok> <tok cat="NNS">trials</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i12"><tok cat="IN">on</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" id="i13" role="SBJ"><cons cat="NP"><tok cat="NN">efficacy</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">judged</tok><cons cat="NP" ref="i13" null="NONE"></cons><cons cat="PP" ref="i12" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@48@@oe@16-12-2010 1037227107@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">variability</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><cons cat="ADVP"><tok cat="RB">even</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="ADJP"><cons cat="ADVP"><tok cat="DT">the</tok> <tok cat="RBS">most</tok> <tok cat="RB">narrowly</tok></cons> <tok cat="VBN">targeted</tok></cons> <tok cat="NNS">agents</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">suggests</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">diseases</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><cons cat="ADJP"><cons cat="ADVP"><tok cat="RB">far</tok> <tok cat="RBR">more</tok></cons> <tok cat="JJ">heterogeneous</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">humans</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="JJ">murine</tok> <tok cat="NNS">counterparts</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1037227108@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i9" role="SBJ"><tok cat="NNS">Clinicians</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">only</tok></cons> <cons cat="ADVP"><tok cat="RB">just</tok></cons> <cons cat="VP"><tok cat="VBG">beginning</tok> <cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">recognize</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">subclinical</tok> <tok cat="NNS">markers</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">response</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="PRP">it</tok></cons> <cons cat="S" ref="i5" null="EXP"></cons></cons><cons cat="VP"><tok cat="MD">may</tok> <cons cat="ADVP"><tok cat="RB">soon</tok></cons> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">possible</tok> <cons cat="S" id="i5"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">predict</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">basis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">genetic</tok> <tok cat="NN">composition</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1037227109@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">For</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">moment</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">field</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">pharmacogenetics</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">embryonic</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1037227110@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">Challenges</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">developing</tok> <cons cat="NP"><tok cat="JJ">new</tok> <tok cat="JJ">therapeutic</tok> <tok cat="NNS">strategies</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">include</tok> <cons cat="S" syn="COOD"><tok cat="RB">not</tok> <tok cat="RB">only</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">identifying</tok> <cons cat="NP"><tok cat="JJ">novel</tok> <tok cat="NNS">agents</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">also</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBG">improving</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">definitions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">clinical</tok> <tok cat="NNS">endpoints</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBG">defining</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">efficacy</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">biologic</tok> <tok cat="NN">level</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1037227111@GENIA Treebank@formal@@1@S@<cons cat="SINV"><cons cat="PP"><cons cat="ADVP"><tok cat="RB">Only</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">considered</tok> <tok cat="NN">evaluation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">clinical</tok> <tok cat="NN">evidence</tok></cons></cons></cons></cons></cons> <tok cat="MD">may</tok> <cons cat="NP" role="SBJ"><tok cat="NNS">clinicians</tok></cons> <cons cat="VP"><tok cat="VB">determine</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><cons cat="WHNP" id="i10"><tok cat="WDT">which</tok> <tok cat="NNS">therapies</tok></cons> <cons cat="S"><cons cat="NP" ref="i10" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">should</tok> <cons cat="VP"><tok cat="VB">remain</tok> <cons cat="NP" role="PRD"><tok cat="NNS">novelties</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><cons cat="WHNP" id="i11"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">should</tok> <cons cat="VP"><tok cat="VB">become</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="VBN">accepted</tok> <tok cat="NN">part</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">armamentarium</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1037352201@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">p70(s6k)</tok></cons> <cons cat="VP"><tok cat="VBZ">integrates</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">phosphatidylinositol</tok> <tok cat="NN">3-kinase</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">rapamycin-regulated</tok> <tok cat="NNS">signals</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">E2F</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1037352202@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">hematopoietic</tok> <tok cat="NN">cytokine</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin-2</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-2</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">uses</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">phosphatidylinositol</tok> <tok cat="NN">3-kinase</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">PI</tok> <tok cat="NN">3-kinase</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="JJ">-induced</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">regulate</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">E2F</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activity</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">critical</tok> <tok cat="NN">cell</tok> <tok cat="NN">cycle</tok> <tok cat="NN">checkpoint</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1037352203@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PI</tok> <tok cat="NN">3-kinase</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBZ">regulates</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">p70(s6k)</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">40S</tok> <tok cat="JJ">ribosomal</tok> <tok cat="NN">protein</tok> <tok cat="NN">S6</tok> <tok cat="NN">kinase</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">response</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" id="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">abrogated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">macrolide</tok></cons> <cons cat="NP"><tok cat="NN">rapamycin</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1037352204@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="DT">This</tok> <tok cat="JJ">immunosuppressive</tok> <tok cat="NN">drug</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">prevent</tok> <cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NN">proliferation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">precise</tok> <tok cat="NN">point</tok></cons> <cons cat="SBAR"><cons cat="WHADVP" id="i5"><tok cat="IN">at</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">rapamycin</tok></cons> <cons cat="VP"><tok cat="VBZ">regulates</tok> <cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NN">cycle</tok> <tok cat="NN">progression</tok></cons> <cons cat="ADVP" ref="i5" null="T"></cons></cons></cons></cons></cons><cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="S"><cons cat="NP" ref="i4" id="i12" role="SBJ" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">yet</tok></cons> <cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">elucidated</tok><cons cat="NP" ref="i12" null="NONE"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1037352205@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i6" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">rapamycin</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok><cons cat="NP" ref="i7" null="RNR"></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">p70(s6k)</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok><cons cat="NP" ref="i7" null="RNR"></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i7"><cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">PI</tok> <tok cat="NN">3-kinase</tok></cons></cons> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">E2Fs</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">characterized</tok><cons cat="NP" ref="i6" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1037352206@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="JJ">present</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-2-</tok> <cons cat="NP" ref="i13" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="NP" id="i13"><tok cat="NN">PI</tok> <tok cat="JJ">3-kinase-induced</tok> <tok cat="NNS">pathways</tok></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">E2F</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">include</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><tok cat="CC">both</tok> <cons cat="ADJP"><tok cat="JJ">rapamycin-resistant</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">rapamycin-sensitive</tok></cons></cons> <tok cat="NNS">components</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1037352207@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">rapamycin-resistant</tok> <tok cat="NN">mutant</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">p70(s6k)</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">could</tok> <cons cat="VP"><tok cat="VB">restore</tok> <cons cat="NP"><tok cat="JJ">rapamycin-suppressed</tok> <tok cat="NN">E2F</tok> <tok cat="NNS">responses</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1037352208@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Thus</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">rapamycin-controlled</tok> <tok cat="NNS">processes</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">E2F</tok> <tok cat="NN">regulation</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">appear</tok> <cons cat="S" role="PRD"><cons cat="NP" ref="i8" id="i9" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">p70(s6k)</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1037352209@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="JJ">rapamycin-resistant</tok> <tok cat="NN">p70(s6k)</tok></cons> <cons cat="VP"><tok cat="MD">could</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">rescue</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">rapamycin</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NN">cycle</tok> <tok cat="NN">entry</tok></cons><tok cat="COMMA">,</tok> <cons cat="ADJP"><tok cat="JJ">consistent</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">involvement</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="ADJP"><cons cat="ADJP"><tok cat="JJ">additional</tok></cons><tok cat="COMMA">,</tok> <cons cat="ADJP"><tok cat="JJ">rapamycin-sensitive</tok></cons></cons> <tok cat="NNS">pathways</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NN">cycle</tok> <tok cat="NN">progression</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1037352210@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="JJ">present</tok> <tok cat="NNS">results</tok></cons> <cons cat="ADVP"><tok cat="RB">thus</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i10" role="SBJ"><tok cat="NN">p70(s6k)</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">able</tok> <cons cat="S"><cons cat="NP" ref="i10" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">regulate</tok> <cons cat="NP"><tok cat="NN">E2F</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VB">provide</tok> <cons cat="NP"><tok cat="JJ">direct</tok> <tok cat="NN">evidence</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">first</tok> <tok cat="NN">time</tok></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">link</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NNS">receptors</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">PI</tok> <tok cat="NN">3-kinase</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">p70(s6k)</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i11"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">regulates</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">crucial</tok> <tok cat="NN">G1</tok> <tok cat="NN">checkpoint</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1037354801@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="NN">SOCS-3</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="NN">tyrosine</tok> <tok cat="JJ">phosphorylated</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">interleukin-2</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">suppresses</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT5</tok> <tok cat="NN">phosphorylation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">lymphocyte</tok> <tok cat="NN">proliferation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1037354802@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="NNS">Members</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP"><tok cat="RB">recently</tok> <tok cat="VBN">discovered</tok></cons> <tok cat="NN">SOCS/CIS/SSI</tok> <tok cat="NN">family</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">proposed</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">regulators</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NN">signaling</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i3" role="SBJ"><cons cat="NP"><tok cat="NNS">targets</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">mechanisms</tok></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">suggested</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="NN">family</tok> <tok cat="NNS">members</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">precise</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">proteins</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">remains</tok> <cons cat="S" role="PRD"><cons cat="NP" ref="i4" id="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">defined</tok><cons cat="NP" ref="i5" null="NONE"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1037354803@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="TO">To</tok> <cons cat="NP"><tok cat="VB">date</tok></cons></cons> <cons cat="NP" id="i6" role="SBJ"><tok cat="DT">no</tok> <tok cat="NN">SOCS</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="ADVP"><tok cat="RB">specifically</tok></cons> <cons cat="VP"><tok cat="VBN">implicated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin-2</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-2</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">signaling</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1037354804@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">report</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">SOCS-3</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">T-cell</tok> <tok cat="NNS">lines</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1037354805@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">SOCS-3</tok> <tok cat="NN">protein</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">detectable</tok> <cons cat="ADVP"><cons cat="ADVP"><tok cat="RB">as</tok> <tok cat="RB">early</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">30</tok> <tok cat="NN">min</tok></cons> <cons cat="PP" adv="TMP"><tok cat="VBG">following</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">stimulation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="NN">CIS</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">seen</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">only</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="JJ">low</tok> <tok cat="NNS">levels</tok></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><tok cat="CD">2</tok> <tok cat="NN">h</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1037354806@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Unlike</tok> <cons cat="NP"><tok cat="NN">CIS</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i8" role="SBJ"><tok cat="NN">SOCS-3</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">rapidly</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="NN">tyrosine</tok> <tok cat="JJ">phosphorylated</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">IL-2</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1037354807@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i9" role="SBJ"><cons cat="NP"><tok cat="NN">Tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">SOCS-3</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">coexpression</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Jak1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Jak2</tok></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="PP"><cons cat="ADVP"><tok cat="RB">only</tok> <tok cat="RB">weakly</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Jak3</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1037354808@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">experiments</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">SOCS-3</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">associated</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Jak1</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><tok cat="NN">Jak1</tok> <tok cat="NN">phosphorylation</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i10" role="SBJ"><tok cat="DT">this</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">markedly</tok></cons> <cons cat="VP"><tok cat="VBN">enhanced</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">receptor</tok> <tok cat="NN">beta</tok> <tok cat="NN">chain</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-2Rbeta</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1037354809@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">following</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">stimulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i11" role="SBJ"><tok cat="NN">SOCS-3</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">able</tok> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">interact</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">receptor</tok> <tok cat="NN">complex</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">particular</tok></cons></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">tyrosine</tok> <tok cat="JJ">phosphorylated</tok> <tok cat="NN">Jak1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-2Rbeta</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1037354810@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Additionally</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">lymphocytes</tok></cons> <cons cat="VP"><tok cat="VBG">expressing</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">SOCS-3</tok></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="NN">CIS</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i12" role="SBJ"><cons cat="NP"><tok cat="JJ">IL-2-induced</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT5b</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">markedly</tok></cons> <cons cat="VP"><tok cat="VBN">reduced</tok><cons cat="NP" ref="i12" null="NONE"></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="EX">there</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">only</tok></cons> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">weak</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">IL-3-mediated</tok> <tok cat="NN">STAT5b</tok></cons> <cons cat="NP"><tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons></cons>@@@@1@32@@oe@16-12-2010 1037354811@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Finally</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i13" role="SBJ"><cons cat="NP"><tok cat="NN">proliferation</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">IL-2-</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-3</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="JJ">inhibited</tok> <cons cat="NP" ref="i13" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">SOCS-3</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1037354812@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i14"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" id="i15" role="SBJ"><tok cat="NN">SOCS-3</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">rapidly</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i15" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">IL-2</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><cons cat="ADVP" ref="i14" null="T"></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i17" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="VBZ">acts</tok> <cons cat="S"><cons cat="NP" ref="i17" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">inhibit</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NNS">responses</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">classical</tok> <tok cat="JJ">negative</tok> <tok cat="NN">feedback</tok> <tok cat="NN">loop</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1037469901@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gamma/delta</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">receptor</tok> <tok cat="JJ">positive</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">pregnancy</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1037469902@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">PROBLEM</tok></cons><tok cat="COLON">:</tok> <cons cat="PP"><tok cat="JJ">Due</tok> <tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">lack</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">classical</tok> <tok cat="NN">HLA</tok> <tok cat="NNS">antigens</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">trophoblast</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i1" role="SBJ"><tok cat="JJ">fetal</tok> <tok cat="NNS">antigens</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">possibly</tok></cons> <cons cat="VP"><tok cat="VBN">presented</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">non</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">major</tok> <tok cat="NN">histocompatibility</tok> <tok cat="NN">complex</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MHC</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="JJ">restricted</tok> <tok cat="NN">way</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1037469903@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Decidual</tok> <tok cat="NN">gammadelta</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBP">increase</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">number</tok></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="NN">pregnancy</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="MD">might</tok> <cons cat="VP"><tok cat="VB">play</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">recognition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">fetal</tok> <tok cat="NNS">antigens</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">determining</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">quality</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">antigens</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1037469904@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NN">study</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">aimed</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">at</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">investigating</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">cell</tok> <tok cat="NN">population</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">progesterone-dependent</tok> <tok cat="NN">immunomodulation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1037469905@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><cons cat="NP"><tok cat="NN">METHOD</tok></cons> <cons cat="PP"><tok cat="IN">OF</tok> <cons cat="NP"><tok cat="NN">STUDY</tok></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="JJ">Peripheral</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">healthy</tok> <tok cat="JJ">pregnant</tok> <tok cat="NNS">women</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">habitual</tok> <tok cat="NNS">aborters</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">tested</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">immunocytochemistry</tok></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">gamma/delta</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">TCR</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">progesterone</tok> <tok cat="NN">receptor</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1037469906@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">investigate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">treatment</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">pan</tok> <tok cat="JJ">anti</tok> <tok cat="NN">gamma/delta</tok> <tok cat="NN">antibody</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="NNS">lymphocytes</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">incubated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP" adv="TMP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="CD">3</tok> <tok cat="NN">hr</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">antibody</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">then</tok></cons> <cons cat="S"><cons cat="NP" syn="COOD" id="i6" role="SBJ"><cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="CD">-10</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-12</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">progesterone-induced</tok> <tok cat="VBG">blocking</tok> <tok cat="NN">factor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">PIBF</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">expression</tok></cons></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">immuno-cytochemistry</tok></cons></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">natural</tok> <tok cat="NN">killer</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NK</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">cell</tok> <tok cat="NN">activity</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">determined</tok><cons cat="NP" ref="i6" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@57@@oe@16-12-2010 1037469907@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">RESULTS</tok></cons><tok cat="COLON">:</tok> <cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">healthy</tok> <tok cat="JJ">pregnant</tok> <tok cat="NNS">women</tok></cons></cons></cons></cons> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">percentage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gamma/delta</tok> <tok cat="JJ">TCR+</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="ADJP" role="PRD"><cons cat="ADJP"><tok cat="JJR">higher</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">P</tok></cons> <cons cat="VP"><tok cat="JJR"><</tok> <cons cat="NP"><tok cat="CD">0.001</tok></cons></cons></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="SBAR"><tok cat="IN">than</tok> <cons cat="FRAG"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">that</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">recurrent</tok> <tok cat="NNS">aborters</tok></cons></cons> <tok cat="CC">or</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">non-pregnant</tok> <tok cat="NNS">individuals</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1037469908@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="CD">Ninety-seven</tok> <tok cat="NN">percent</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gamma/delta</tok> <tok cat="JJ">TCR+</tok> <tok cat="NN">pregnancy</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">expressed</tok> <cons cat="NP"><tok cat="NN">progesterone</tok> <tok cat="NN">receptor</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1037469909@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">specific</tok> <tok cat="NN">antibody</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">gamma/delta</tok> <tok cat="NN">TCR</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">PIBF-</tok></cons> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="NP"><tok cat="NN">IL-10</tok></cons></cons> <tok cat="NN">production</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="VBD">increased</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NK</tok> <tok cat="NN">activity</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-12</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1037469910@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">CONCLUSIONS</tok></cons><tok cat="COLON">:</tok> <cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gamma/delta</tok> <tok cat="JJ">TCR-bearing</tok> <tok cat="NNS">lymphocytes</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">progesterone-dependent</tok> <tok cat="NN">immunomodulation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1037653101@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Expression</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">role</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PML</tok> <tok cat="NN">gene</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">adult</tok> <tok cat="NN">hematopoiesis</tok></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">functional</tok> <tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">PML</tok> <cons cat="NP" ref="i2" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Rb</tok> <cons cat="NP" ref="i2" null="RNR"></cons></cons><cons cat="NP" id="i2"><tok cat="NNS">proteins</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">erythropoiesis</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1037653102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">PML</tok> <tok cat="NN">gene</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">investigated</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">purified</tok> <tok cat="JJ">early</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">hematopoietic</tok> <tok cat="NN">progenitor</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">HPCs</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">unilineage</tok> <tok cat="JJ">erythroid</tok></cons> <tok cat="CC">or</tok> <cons cat="ADJP"><tok cat="JJ">granulocytic</tok></cons></cons> <tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1037653103@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" id="i5" role="SBJ"><cons cat="NP"><tok cat="NN">PML</tok> <tok cat="NN">mRNA</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">protein</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="FRAG"><cons cat="ADVP"><tok cat="RB">barely</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">detectable</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">quiescent</tok> <tok cat="NNS">HPCs</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">consistently</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">growth</tok> <tok cat="NN">factor</tok> <tok cat="NN">stimulation</tok></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">granulocytic</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><cons cat="NP" id="i4"><tok cat="NN">lineage</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1037653104@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="ADVP"><tok cat="RB">Thereafter</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i6" role="SBJ"><tok cat="NN">PML</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">downmodulated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP" adv="TMP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">late</tok> <tok cat="JJ">granulocytic</tok> <tok cat="NN">maturation</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">sustainably</tok></cons> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">erythroid</tok> <tok cat="NN">pathway</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1037653105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="JJ">functional</tok> <tok cat="NNS">studies</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i8" role="SBJ"><tok cat="NN">PML</tok> <tok cat="NN">expression</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">antisense</tok> <tok cat="NNS">oligomers</tok></cons> <cons cat="VP"><tok cat="VBG">targeting</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">PML</tok> <tok cat="NN">mRNA</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">alpha-PML</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1037653106@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="ADVP"><tok cat="RB">Interestingly</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">early</tok> <tok cat="NN">treatment</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">day</tok> <tok cat="CD">0</tok> <tok cat="NNS">HPCs</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">alpha-PML</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">reduced</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">number</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><tok cat="CC">both</tok> <cons cat="ADJP"><tok cat="JJ">erythroid</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">granulocytic</tok></cons></cons> <tok cat="NNS">colonies</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">late</tok> <tok cat="NN">treatment</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">day</tok> <tok cat="CD">5</tok> <tok cat="NN">culture</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBD">reduced</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">erythroid</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="ADJP"><tok cat="JJ">granulocytic</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="NN">clonogenesis</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1037653107@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i9" role="SBJ"><tok cat="NN">PML</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">early</tok> <tok cat="NN">hematopoiesis</tok></cons> <tok cat="CC">and</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">erythroid</tok><cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="JJ">granulocytic</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><tok cat="NN">maturation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1037653108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">pattern</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">PML</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NN">hematopoiesis</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">mimics</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">that</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">retinoblastoma</tok></cons> <cons cat="NP"><tok cat="NN">pRb</tok> <tok cat="CD">105</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1037653109@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Combined</tok> <tok cat="NN">treatment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">HPCs</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">alpha-PML</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">alpha-Rb</tok> <tok cat="NNS">oligomers</tok></cons></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">PML</tok> <cons cat="NP" ref="i10" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Rb</tok> <cons cat="NP" ref="i10" null="RNR"></cons></cons><cons cat="NP" id="i10"><tok cat="NN">protein</tok> <tok cat="NN">expression</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">completely</tok></cons> <cons cat="VP"><tok cat="VBD">blocked</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">colony</tok> <tok cat="NN">development</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1037653110@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" id="i11" role="SBJ"><cons cat="NP"><tok cat="NN">PML</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">pRb</tok> <tok cat="CD">105</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">co-immunoprecipitated</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cellular</tok> <tok cat="NNS">lysates</tok></cons> <cons cat="VP"><tok cat="VBN">derived</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">precursors</tok></cons></cons></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">indicating</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">this</tok> <tok cat="JJ">functional</tok> <tok cat="NN">interaction</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">have</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">biochemical</tok> <tok cat="NN">basis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1037653111@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">key</tok> <tok cat="JJ">functional</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PML</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">early</tok> <tok cat="NN">hematopoiesis</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">late</tok> <tok cat="NN">erythropoiesis</tok></cons></cons></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" id="i12" role="SBJ"><tok cat="DT">the</tok> <tok cat="JJ">latter</tok> <tok cat="NN">phenomenon</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="JJ">related</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">molecular</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">functional</tok></cons></cons> <tok cat="NN">interaction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">PML</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">pRb</tok> <tok cat="CD">105</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1037707501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PPARalpha</tok> <tok cat="NNS">activators</tok></cons> <cons cat="VP"><tok cat="VBP">inhibit</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cytokine-induced</tok> <tok cat="JJ">vascular</tok> <tok cat="NN">cell</tok> <tok cat="NN">adhesion</tok> <tok cat="NN">molecule-1</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1037707502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NN">BACKGROUND</tok></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Adhesion</tok> <tok cat="NN">molecule</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NN">cell</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">EC</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">surface</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">critical</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">leukocyte</tok> <tok cat="NN">recruitment</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">atherosclerotic</tok> <tok cat="NNS">lesions</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1037707503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJR">Better</tok> <tok cat="NN">understanding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">adhesion</tok> <tok cat="NNS">molecules</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">ECs</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">provide</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">important</tok> <tok cat="NN">insight</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="NN">plaque</tok> <tok cat="NN">formation</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1037707504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Peroxisome</tok> <tok cat="JJ">proliferator-activated</tok> <tok cat="NN">receptor-alpha</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">PPARalpha</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">member</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">receptor</tok> <tok cat="NN">family</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">regulates</tok> <cons cat="NP"><tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">certain</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">fatty</tok> <tok cat="NNS">acids</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">fibric</tok> <tok cat="NN">acid</tok> <tok cat="NNS">derivatives</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1037707505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="JJ">present</tok> <tok cat="NN">study</tok></cons> <cons cat="VP"><tok cat="VBD">investigated</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">PPARalpha</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">ECs</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">vascular</tok> <tok cat="NN">cell</tok> <tok cat="NN">adhesion</tok> <tok cat="NN">molecule-1</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">VCAM-1</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1037707506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">METHODS</tok></cons> <tok cat="CC">AND</tok> <cons cat="NP"><tok cat="NNS">RESULTS</tok></cons></cons><tok cat="COLON">:</tok> <cons cat="NP" role="SBJ"><tok cat="NN">Immunohistochemistry</tok></cons> <cons cat="VP"><tok cat="VBD">revealed</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">human</tok> <tok cat="NN">carotid</tok> <tok cat="NN">artery</tok> <tok cat="NNS">ECs</tok></cons> <cons cat="VP"><tok cat="VBP">express</tok> <cons cat="NP"><tok cat="NN">PPARalpha</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1037707507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Pretreatment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">cultured</tok> <tok cat="JJ">human</tok> <tok cat="NNS">ECs</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">PPARalpha</tok> <tok cat="NNS">activators</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">fenofibrate</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">WY14643</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><tok cat="JJ">TNF-alpha-induced</tok> <tok cat="NN">VCAM-1</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="NN">time-</tok> <cons cat="ADJP" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">concentration-dependent</tok></cons></cons> <tok cat="NN">manner</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">effect</tok></cons> <cons cat="VP"><tok cat="RB">not</tok> <tok cat="VBN">seen</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">PPARgamma</tok> <tok cat="NNS">activators</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1037707508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="DT">Both</tok> <tok cat="NN">PPARalpha</tok> <tok cat="NNS">activators</tok></cons> <cons cat="VP"><tok cat="VBD">decreased</tok> <cons cat="NP"><tok cat="JJ">cytokine-induced</tok> <tok cat="NN">VCAM-1</tok> <tok cat="NN">mRNA</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">altering</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">mRNA</tok> <tok cat="NN">half-life</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1037707509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Transient</tok> <tok cat="NN">transfection</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">deletional</tok> <tok cat="NN">VCAM-1</tok> <tok cat="NN">promoter</tok> <tok cat="NNS">constructs</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">electrophoretic</tok> <tok cat="NN">mobility</tok> <tok cat="NN">shift</tok> <tok cat="NNS">assays</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="NN">fenofibrate</tok></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><tok cat="NN">VCAM-1</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">part</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">inhibiting</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1037707510@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Finally</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">PPARalpha</tok> <tok cat="NNS">activators</tok></cons> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBD">reduced</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">adhesion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">U937</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="VBN">cultured</tok> <tok cat="JJ">human</tok> <tok cat="NNS">ECs</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1037707511@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP"><tok cat="NNS">CONCLUSIONS</tok></cons><tok cat="COLON">:</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Human</tok> <tok cat="NNS">ECs</tok></cons> <cons cat="VP"><tok cat="VBP">express</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">PPARalpha</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <cons cat="ADJP"><tok cat="RB">potentially</tok> <tok cat="JJ">important</tok></cons> <tok cat="NN">regulator</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">atherogenesis</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">VCAM-1</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1037707512@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Such</tok> <tok cat="NNS">findings</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">implications</tok></cons> <cons cat="PP"><tok cat="VBG">regarding</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">clinical</tok> <tok cat="NN">use</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">lipid-lowering</tok> <tok cat="NNS">agents</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">like</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">fibric</tok> <tok cat="NNS">acids</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><tok cat="NN">PPARalpha</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1037741101@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="JJ">intracellular</tok> <tok cat="NN">parasite</tok></cons> <cons cat="NP"><tok cat="FW">Theileria</tok> <tok cat="FW">parva</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">protects</tok> <cons cat="NP"><tok cat="JJ">infected</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1037741102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i13" role="SBJ"><tok cat="NNS">Parasites</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">evolved</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">plethora</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">strategies</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" ref="i13" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">ensure</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">survival</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1037741103@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="JJ">intracellular</tok> <tok cat="NN">parasite</tok></cons> <cons cat="NP"><tok cat="FW">Theileria</tok> <tok cat="FW">parva</tok></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">secures</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">propagation</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">spreads</tok> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">infected</tok> <tok cat="NN">animal</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP" syn="COOD"><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBG">infecting</tok> <cons cat="NP" ref="i14" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBG">transforming</tok> <cons cat="NP" ref="i14" null="RNR"></cons></cons><cons cat="NP" id="i14"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBG">inducing</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="JJ">continuous</tok> <tok cat="NN">proliferation</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBG">rendering</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">them</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">metastatic</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1037741104@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="JJ">previous</tok> <tok cat="NN">work</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">parasite</tok></cons> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">constitutive</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">inducing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">constitutive</tok> <tok cat="NN">degradation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">cytoplasmic</tok> <tok cat="NNS">inhibitors</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1037741105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">biological</tok> <tok cat="NN">significance</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="FW">T.</tok> <tok cat="JJ">parva-infected</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">has</tok> <tok cat="RB">not</tok> <cons cat="ADVP"><tok cat="RB">yet</tok></cons> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">defined</tok><cons cat="NP" ref="i3" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1037741106@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">Cells</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" id="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">transformed</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">viruses</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NNS">oncogenes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">persist</tok> <cons cat="SBAR" func="ADV"><cons cat="ADVP"><tok cat="RB">only</tok></cons> <tok cat="IN">if</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="PRP">they</tok></cons> <cons cat="VP"><tok cat="VBP">manage</tok> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">avoid</tok> <cons cat="NP"><tok cat="NN">destruction</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">apoptotic</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><cons cat="WHNP" id="i7"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i7" id="i8" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">transformation</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><cons cat="WHNP" id="i9"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">contribute</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">maintain</tok> <cons cat="NP"><tok cat="JJ">cellular</tok> <tok cat="NN">homeostasis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1037741107@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">now</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i10" role="SBJ"><tok cat="JJ">parasite-induced</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">crucial</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">survival</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="FW">T.</tok> <tok cat="JJ">parva-transformed</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i10" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">conveying</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">protection</tok></cons> <cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">apoptotic</tok> <tok cat="NN">signal</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i11"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">accompanies</tok> <cons cat="NP"><tok cat="JJ">parasite-mediated</tok> <tok cat="NN">transformation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1037741108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Consequently</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">dominant</tok> <tok cat="JJ">negative</tok> <tok cat="JJ">mutant</tok> <tok cat="NNS">forms</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">components</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok> <tok cat="NN">pathway</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IkappaBalpha</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">p65</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBP">prompt</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">rapid</tok> <tok cat="NN">apoptosis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="FW">T.</tok> <tok cat="JJ">parva-transformed</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1037741109@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">offer</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">important</tok> <tok cat="NNS">insights</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="JJ">parasite</tok> <tok cat="NN">survival</tok> <tok cat="NNS">strategies</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">parasite-induced</tok> <tok cat="JJ">constitutive</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">essential</tok> <tok cat="NN">step</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">maintaining</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBN">transformed</tok> <tok cat="NN">phenotype</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">infected</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1037889501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Downregulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Wilms</tok><tok cat="POS">'</tok> <tok cat="NN">tumor</tok> <tok cat="NN">gene</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">WT1</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">prerequisite</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">erythroid</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">megakaryocytic</tok> <cons cat="NP" ref="i8" null="RNR"></cons></cons><cons cat="NP" id="i8"><tok cat="NN">differentiation</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">leukemic</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok> <tok cat="NN">K562</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1037889502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Wilms</tok><tok cat="POS">'</tok> <tok cat="NN">tumor</tok> <tok cat="NN">gene</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">WT1</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">encodes</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">zinc</tok> <tok cat="NN">finger</tok> <tok cat="NN">type</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1037889503@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="JJ">high</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">WT1</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">range</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">acute</tok> <tok cat="NNS">leukemias</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NN">WT1</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">downregulated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">induced</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="JJ">leukemic</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1037889504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Overexpression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">WT1</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="JJ">myeloid</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">confers</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">resistance</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">differentiation</tok> <tok cat="NN">induction</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1037889505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">observations</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">high</tok> <tok cat="NN">WT1</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">hematopoietic</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">incompatible</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1037889506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">each</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="CD">four</tok> <tok cat="JJ">different</tok> <tok cat="NNS">isoforms</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">WT1</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">constitutively</tok></cons> <cons cat="VP"><tok cat="VBN">overexpressed</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">leukemic</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok> <tok cat="NN">K562</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1037889507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">K562</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">express</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">endogenous</tok> <tok cat="NN">WT1</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" id="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">downregulated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="VBN">induced</tok> <tok cat="NN">differentiation</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">along</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">erythroid</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">megakaryocytic</tok></cons></cons> <tok cat="NNS">pathways</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1037889508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">now</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">forced</tok> <tok cat="JJ">exogenous</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="CD">four</tok> <tok cat="JJ">different</tok> <tok cat="NNS">isoforms</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">WT1</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">K562</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">differentiation</tok> <tok cat="NN">response</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">as</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">judged</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><cons cat="NP"><cons cat="NP"><tok cat="NN">accumulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">hemoglobin</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">hemin</tok></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">megakaryocytic</tok> <tok cat="NN">cell</tok> <tok cat="NN">surface</tok> <tok cat="NNS">markers</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">12-O-tetradecanoylphorbol-13-acetate</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">TPA</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@50@@oe@16-12-2010 1037889509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">conclude</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">downregulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">WT1</tok></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">induced</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">K562</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">prerequisite</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">erythroid</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">megakaryocytic</tok> <cons cat="NP" ref="i6" null="RNR"></cons></cons><cons cat="NP" id="i6"><tok cat="NN">differentiation</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1037889601@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">Signal</tok> <tok cat="NN">transduction</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">human</tok> <tok cat="NNS">monocytes</tok></cons> <cons cat="VP"><tok cat="VBN">stimulated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><cons cat="NP"><tok cat="NNS">cytokines</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">mediators</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">comparative</tok> <tok cat="NN">study</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">human</tok> <tok cat="NNS">neutrophils</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="VBN">transformed</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">putative</tok> <tok cat="NNS">roles</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">functionality</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">biology</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1037889602@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Granulocyte-macrophage</tok> <tok cat="JJ">colony-stimulating</tok> <tok cat="NN">factor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">GM-CSF</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CD">-3</tok></cons></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">92-kDa</tok> <tok cat="NN">protein</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">human</tok> <tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1037889603@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">identified</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="JJ">92-kDa</tok> <tok cat="NN">protein</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP" syn="COOD"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STATs1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="CD">3</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="CD">6</tok></cons></cons> <tok cat="CC">nor</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">c-fes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">vav</tok> <tok cat="NN">protooncogene</tok> <tok cat="NNS">products</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">demonstrated</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">translocation</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nucleus</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">enhancement</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">specific</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">capacity</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">potentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">trancriptional</tok> <tok cat="NN">activity</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">GM-CSF</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@47@@oe@16-12-2010 1037889604@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">N-formyl-methionyl-leucyl-phenylalanine</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">FMLP</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">phorbol</tok> <tok cat="NN">myristate</tok> <tok cat="NN">acetate</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">PMA</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">42-</tok> <cons cat="NP" ref="i1" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="NP" id="i1"><tok cat="JJ">44-kDa</tok> <tok cat="NNS">proteins</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" id="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">identified</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">extracellular</tok> <tok cat="JJ">signal-regulated</tok> <tok cat="NN">kinase</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">ERK</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1037889605@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">marked</tok> <tok cat="NN">contrast</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">neutrophils</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">MO7e</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">GM-CSF</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">ERK</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1037889606@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">Among</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">upstream</tok> <tok cat="VBG">signaling</tok> <tok cat="NNS">molecules</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">ERK</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="NN">Shc</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">constitutively</tok></cons> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Grb2</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">tyrosine-phosphorylated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><cons cat="NP"><tok cat="NN">GM-CSF</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">FMLP</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i5" role="SBJ"><cons cat="NP"><tok cat="NN">Sos1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">c-Raf-1</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">phosphorylated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">GM-CSF</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-3</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">TNF</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">FMLP</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="PDT">all</tok> <tok cat="DT">these</tok> <tok cat="VBG">signaling</tok> <tok cat="NNS">molecules</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBN">affected</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP" ref="i8" null="RNR"></cons></cons><tok cat="CC">and/or</tok> <cons cat="VP"><tok cat="VBN">utilized</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP" ref="i8" null="RNR"></cons></cons><cons cat="PP" id="i8"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">GM-CSF</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">MO7e</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@56@@oe@16-12-2010 1037889607@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">contrast</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NNS">neutrophils</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" id="i9" role="SBJ"><tok cat="NN">p38</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">constitutively</tok></cons> <cons cat="VP"><tok cat="VBN">phosphorylated</tok> <cons cat="NP" ref="i9" null="NONE"></cons></cons></cons></cons><tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i10" role="SBJ"><cons cat="NP"><tok cat="JJ">agonist-dependent</tok> <tok cat="NN">phosphorylation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">activation</tok></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1037889608@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i11" role="SBJ"><cons cat="NP"><tok cat="NN">Superoxide</tok> <tok cat="NN">release</tok></cons> <cons cat="VP"><tok cat="VBN">stimulated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">FMLP</tok></cons></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">partially</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">PD98059</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">SB203580</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">specific</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">ERK</tok> <cons cat="NP" ref="i12" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">p38</tok> <cons cat="NP" ref="i12" null="RNR"></cons></cons><cons cat="NP" id="i12"><tok cat="NN">pathway</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">almost</tok> <tok cat="RB">completely</tok></cons> <cons cat="VP"><tok cat="VBN">inhibited</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">combination</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">both</tok> <tok cat="NNS">inhibitors</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">PMA-induced</tok> <tok cat="NN">superoxide</tok> <tok cat="NN">release</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">resistant</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">these</tok> <tok cat="CD">two</tok> <tok cat="NNS">inhibitors</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@47@@oe@16-12-2010 1037889609@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">PD98059</tok></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">GM-CSF-dependent</tok> <tok cat="NN">proliferation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">MO7e</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@8@@oe@16-12-2010 1037889610@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Present</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">trancriptional</tok> <tok cat="NNS">roles</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT5</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">functional</tok> <tok cat="NNS">roles</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">ERK</tok></cons> <tok cat="CC">and/or</tok> <cons cat="NP"><tok cat="NN">p38</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">human</tok> <tok cat="NNS">monocytes</tok></cons> <cons cat="VP"><tok cat="VBN">stimulated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="JJ">physiological</tok> <tok cat="JJ">receptor-mediated</tok> <tok cat="NNS">agonists</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">GM-CSF</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">FMLP</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1037889611@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i14" role="SBJ"><cons cat="NP"><tok cat="JJ">Possible</tok> <tok cat="NNS">roles</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">ERK</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">proliferation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBN">transformed</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">suggested</tok><cons cat="NP" ref="i14" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1038091501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Tyrphostin</tok> <tok cat="NN">AG-490</tok></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">cytokine-mediated</tok> <tok cat="NN">JAK3/STAT5a/b</tok> <tok cat="NN">signal</tok> <tok cat="NN">transduction</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cellular</tok> <tok cat="NN">proliferation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">antigen-activated</tok> <tok cat="JJ">human</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1038091502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Janus</tok> <tok cat="NN">kinase</tok> <tok cat="CD">3</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">JAK3</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">cytoplasmic</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">kinase</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">development</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NNS">cytokines</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">utilize</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin-2</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-2</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">receptor</tok> <tok cat="JJ">common</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gamma</tok> <tok cat="NN">chain</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">gamma(c)</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1038091503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="JJ">Genetic</tok> <tok cat="NN">inactivation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">JAK3</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">manifested</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">severe</tok> <tok cat="JJ">combined</tok> <tok cat="NN">immunodeficiency</tok> <tok cat="NN">disease</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">SCID</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">humans</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">mice</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1038091504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">suggested</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">JAK3</tok></cons> <cons cat="VP"><tok cat="VBZ">represents</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">pharmacological</tok> <tok cat="NN">target</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i9" null="ZERO"></cons><cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">control</tok> <cons cat="NP"><tok cat="JJ">certain</tok> <tok cat="JJ">lymphoid-derived</tok> <tok cat="NNS">diseases</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1038091505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">provide</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">novel</tok> <tok cat="NN">evidence</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">AG-490</tok></cons> <cons cat="ADVP"><tok cat="RB">potently</tok></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">autokinase</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">JAK3</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">tyrosine</tok> <tok cat="NN">phosphorylation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NN">binding</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">signal</tok> <tok cat="NN">transducer</tok> <tok cat="CC">and</tok> <tok cat="NN">activator</tok> <tok cat="IN">of</tok> <tok cat="NN">transcription</tok> <tok cat="NN">5a</tok> <tok cat="CC">and</tok> <tok cat="NN">5b</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">STAT5a/b</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1038091506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="JJ">Similar</tok> <tok cat="JJ">inhibitory</tok> <tok cat="NNS">effects</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="NNS">cytokines</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">use</tok> <cons cat="NP"><tok cat="NN">gamma(c)</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1038091507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">AG-490</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">IL-2-mediated</tok> <tok cat="JJ">proliferative</tok> <tok cat="NN">growth</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">IC50)</tok> <tok cat="JJ">=</tok> <tok cat="CD">25</tok> <tok cat="NN">microM</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">partially</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="JJ">recoverable</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1038091508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="DT">this</tok> <tok cat="NN">inhibitor</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">prevented</tok> <cons cat="NP"><tok cat="NN">tetanus</tok> <tok cat="NN">toxoid</tok> <tok cat="JJ">antigen-specific</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">proliferation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">expansion</tok></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBD">failed</tok> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">block</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Zap70</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">p56Lck</tok></cons></cons></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">anti-CD3</tok> <tok cat="NN">stimulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1038091509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" ref="i8" id="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">Taken</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">together</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i8" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">AG-490</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">JAK3-mediated</tok> <tok cat="NN">Type</tok> <tok cat="CD">II</tok> <tok cat="NN">signaling</tok> <tok cat="NN">pathway</tok></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="JJ">receptor-derived</tok> <tok cat="NN">Type</tok> <tok cat="CD">I</tok> <tok cat="NN">pathway</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">possesses</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">therapeutic</tok> <tok cat="NN">potential</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="JJ">cell-derived</tok> <tok cat="NNS">pathologies</tok></cons> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">graft-versus-host</tok> <tok cat="NN">disease</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">allergy</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">autoimmune</tok> <tok cat="NNS">disorders</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1038150001@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Genetic</tok> <tok cat="NN">evidence</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">additional</tok> <tok cat="NN">factor</tok></cons> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">erythropoietin-induced</tok> <tok cat="NN">signal</tok> <tok cat="NN">transduction</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1038150002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" id="i1" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Erythropoietin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">EPO</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">receptor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">EPOR</tok></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">development</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">mature</tok> <tok cat="NNS">erythrocytes</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1038150003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP" adv="TMP"><tok cat="IN">After</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">ligand</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">EPOR</tok></cons> <cons cat="VP"><tok cat="VBZ">activates</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">variety</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">signaling</tok> <tok cat="NNS">pathways</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="ADVP"><tok cat="RB">ultimately</tok></cons> <cons cat="VP"><tok cat="VBP">control</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cellular</tok> <tok cat="NN">proliferation</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">survival</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">specific</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1038150004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR"><tok cat="IN">Although</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="JJ">erythroid</tok> <tok cat="NNS">progenitors</tok></cons> <cons cat="VP"><tok cat="VBP">appear</tok> <cons cat="S" role="PRD"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP"><cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">principal</tok> <tok cat="JJ">EPO-responsive</tok> <tok cat="NN">cell</tok> <tok cat="NN">type</tok></cons> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vivo</tok></cons></cons> <cons cat="PP"><tok cat="JJ">due</tok> <tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">restricted</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">EPOR</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i6" role="SBJ"><cons cat="NP" id="i5"><tok cat="JJ">many</tok> <tok cat="NN">growth</tok> <tok cat="JJ">factor-dependent</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons> <cons cat="VP"><tok cat="VBG">expressing</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">EPOR</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">respond</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">EPO</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">activating</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">many</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="DT">all</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">pathways</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1038150005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">present</tok> <tok cat="NN">study</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">identified</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">cellular</tok> <tok cat="NN">context</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin-2</tok></cons> <cons cat="PRN"><tok cat="LRB">[</tok><cons cat="NP"><tok cat="NN">IL-2</tok></cons><tok cat="RRB">]</tok></cons></cons><tok cat="JJ">-dependent</tok> <tok cat="NN">HT-2</tok> <tok cat="NN">line</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="SBAR"><cons cat="WHPP" id="i8"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" id="i9" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">EPO</tok> <tok cat="NN">stimulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">EPOR</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">fails</tok> <cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">support</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">cellular</tok> <tok cat="NN">proliferation</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">STAT-5</tok> <tok cat="NN">induction</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">MAPK</tok> <tok cat="NN">activation</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">despite</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">efficient</tok> <tok cat="NN">phosphorylation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">EPOR</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">JAK2</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">apoptosis</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">withdrawal</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-2</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><cons cat="PP" ref="i8" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@59@@oe@16-12-2010 1038150006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Interestingly</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i10"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">fused</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">HT-2</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBG">expressing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">EPOR</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Ba/F3</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">complementation</tok> <tok cat="NN">assay</tok></cons></cons></cons></cons><cons cat="ADVP" ref="i10" null="T"></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="VBG">resulting</tok> <tok cat="NN">hybridomas</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">proliferated</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">potently</tok></cons> <tok cat="VBD">activated</tok> <cons cat="NP" ref="i4" null="RNR"></cons></cons><cons cat="NP" syn="COOD" id="i4"><cons cat="NP"><tok cat="NN">STAT-5</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">MAPK</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">EPO</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1038150007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i11" role="SBJ"><tok cat="DT">an</tok> <tok cat="JJ">unidentified</tok> <tok cat="JJ">cellular</tok> <tok cat="NN">factor</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">needed</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">mediate</tok> <cons cat="NP"><tok cat="NN">signaling</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">EPOR</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1038150008@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">Ba/F3</tok> <tok cat="NNS">cells</tok></cons> <cons cat="ADVP"><tok cat="RB">apparently</tok></cons> <cons cat="VP"><tok cat="VBP">express</tok> <cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">factor</tok><cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">s</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">somatic</tok> <tok cat="NNS">fusions</tok></cons></cons> <cons cat="VP"><tok cat="MD">can</tok><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">therefore</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VB">confer</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">EPO-responsiveness</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">HT-2</tok> <tok cat="NNS">cells</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i12"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i12" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">lack</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">factor</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1038150101@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" id="i1" role="SBJ"><cons cat="NP"><tok cat="NN">GATA-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">erythropoietin</tok></cons></cons> <cons cat="VP"><tok cat="VBP">cooperate</tok> <cons cat="S"><cons cat="NP" ref="i1" id="i11" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">promote</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">cell</tok> <tok cat="NN">survival</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">regulating</tok> <cons cat="NP"><tok cat="NN">bcl-xL</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1038150102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">essential</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NN">erythropoiesis</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@10@@oe@16-12-2010 1038150103@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">By</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">examining</tok> <cons cat="PP"><tok cat="IN">in</tok> <tok cat="JJ">vitro-differentiated</tok> <tok cat="JJ">embryonic</tok> <tok cat="NN">stem</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="ADVP"><tok cat="RB">previously</tok></cons> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><tok cat="VBN">committed</tok> <tok cat="JJ">erythroid</tok> <tok cat="NNS">precursors</tok></cons> <cons cat="VP"><tok cat="VBP">fail</tok> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">complete</tok> <cons cat="NP"><tok cat="NN">maturation</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">instead</tok></cons> <cons cat="VP"><tok cat="VBP">undergo</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1038150104@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NNS">mechanisms</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i4"><tok cat="IN">by</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">GATA-1</tok></cons> <cons cat="VP"><tok cat="VBZ">controls</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">survival</tok></cons> <cons cat="PP" ref="i4" null="T"></cons></cons></cons></cons></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="JJ">unknown</tok><cons cat="NP" ref="i3" null="NONE"></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1038150105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">report</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">GATA-1</tok></cons> <cons cat="ADVP"><tok cat="RB">strongly</tok></cons> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">anti-apoptotic</tok> <tok cat="NN">protein</tok></cons> <cons cat="NP"><tok cat="NN">bcl-xL</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">related</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">bcl-2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">mcl-1</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1038150106@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="ADJP" role="PRD"><tok cat="JJ">Consistent</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">bcl-xL</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">mediating</tok> <cons cat="NP"><tok cat="JJ">GATA-1-induced</tok> <tok cat="JJ">erythroid</tok> <tok cat="NN">cell</tok> <tok cat="NN">survival</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><tok cat="FW">in</tok> <tok cat="JJ">vitro-differentiated</tok> <tok cat="JJ">bcl-xL-/-</tok> <tok cat="JJ">embryonic</tok> <tok cat="NN">stem</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">fail</tok> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">generate</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">viable</tok> <tok cat="JJ">mature</tok> <tok cat="JJ">definitive</tok> <tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">phenotype</tok></cons> <cons cat="VP"><tok cat="VBG">resembling</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">that</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">GATA-1</tok> <tok cat="NN">gene</tok> <tok cat="NN">disruption</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1038150107@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">erythropoietin</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i7"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i7" id="i8" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">cell</tok> <tok cat="NN">survival</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">cooperates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">GATA-1</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">stimulate</tok> <cons cat="NP"><tok cat="NN">bcl-xL</tok> <tok cat="NN">gene</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP" ref="i9" null="RNR"></cons></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">maintain</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NN">cell</tok> <tok cat="NN">viability</tok></cons> <cons cat="PP" ref="i9" null="RNR"></cons></cons></cons><cons cat="PP" id="i9" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="JJ">terminal</tok> <tok cat="NN">maturation</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1038150108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Together</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRPP">our</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">bcl-xL</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">essential</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">erythroid</tok> <tok cat="NN">development</tok></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">hierarchy</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i10"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">bcl-xL</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">critical</tok> <tok cat="JJ">downstream</tok> <tok cat="NN">effector</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">GATA-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">erythropoietin-mediated</tok> <tok cat="NNS">signals</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1038165501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="VP"><tok cat="VBZ">functions</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="CC">both</tok> <tok cat="DT">a</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">proapoptotic</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">antiapoptotic</tok></cons></cons> <tok cat="JJ">regulatory</tok> <tok cat="NN">factor</tok></cons> <cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">single</tok> <tok cat="NN">cell</tok> <tok cat="NN">type</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1038165502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Recently</tok></cons> <cons cat="NP" id="i2" role="SBJ"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="NP" ref="i2" id="i1" null="NONE"></cons><cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">have</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><tok cat="CC">both</tok> <cons cat="ADJP"><tok cat="JJ">proapoptotic</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">antiapoptotic</tok></cons></cons> <tok cat="NNS">functions</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1038165503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NNS">hybridomas</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD" role="SBJ"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NNS">activators</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">glucocorticoids</tok></cons></cons> <cons cat="VP"><tok cat="VBP">induce</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1038165504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">blockade</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activity</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dominant</tok> <tok cat="JJ">negative</tok> <tok cat="NN">IkappaBalpha</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">opposite</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="CD">two</tok> <tok cat="JJ">apoptotic</tok> <tok cat="NNS">signals</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1038165505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Treatment</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">PMA</tok></cons> <tok cat="CC">plus</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">ionomycin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">P/I</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">results</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">upregulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Fas</tok> <tok cat="NN">Ligand</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">FasL</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1038165506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activity</tok></cons></cons></cons> <cons cat="VP"><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP"><tok cat="NN">P/I</tok> <tok cat="JJ">mediated</tok></cons> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">FasL</tok> <tok cat="NN">mRNA</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">decreases</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">level</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">cultures</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">thus</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">establishing</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">proapoptotic</tok> <tok cat="NN">factor</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">context</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1038165507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Conversely</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">confers</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">tenfold</tok> <tok cat="NN">increase</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">glucocorticoid</tok> <tok cat="JJ">mediated</tok> <tok cat="NN">apoptosis</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">establishing</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBZ">functions</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">antiapoptotic</tok> <tok cat="NN">factor</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1038165508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">conclude</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><tok cat="DT">a</tok> <tok cat="JJ">context-dependent</tok> <tok cat="NN">apoptosis</tok> <tok cat="NN">regulator</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@10@@oe@16-12-2010 1038165509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NN">data</tok></cons> <cons cat="VP"><tok cat="VBZ">suggests</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">function</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">antiapoptotic</tok> <tok cat="NN">factor</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">thymocytes</tok></cons></cons></cons></cons> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">functioning</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">proapoptotic</tok> <tok cat="NN">factor</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">mature</tok> <tok cat="JJ">peripheral</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1038339701@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">3-deazaadenosine</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">S-adenosylhomocysteine</tok> <tok cat="NN">hydrolase</tok> <tok cat="NN">inhibitor</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">dual</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">regulation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1038339702@GENIA Treebank@formal@@1@S@<cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">Inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activity</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">promotion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IkappaBalpha</tok> <tok cat="NN">degradation</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1038339703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Previously</tok></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">reported</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">3-deazaadenosine</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">DZA</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><tok cat="DT">a</tok> <cons cat="NP"><tok cat="JJ">potent</tok> <tok cat="NN">inhibitor</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">substrate</tok></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">S-adenosylhomocysteine</tok> <tok cat="NN">hydrolase</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">bacterial</tok> <tok cat="JJ">lipopolysaccharide-induced</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor-alpha</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">interleukin-1beta</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">mouse</tok> <tok cat="NN">macrophage</tok> <tok cat="NN">RAW</tok> <tok cat="CD">264.7</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1038339704@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">DZA</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">factor-kappaB</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">regulation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1038339705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">DZA</tok></cons> <cons cat="VP"><tok cat="VBZ">inhibits</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">hindrance</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">p65</tok> <tok cat="LRB">(</tok><tok cat="NN">Rel-A</tok><tok cat="RRB">)</tok> <tok cat="NN">phosphorylation</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">reduction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1038339706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">inhibitory</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">DZA</tok></cons></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activity</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">potentiated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">homocysteine</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1038339707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" id="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">Taken</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">together</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">DZA</tok></cons> <cons cat="VP"><tok cat="VBZ">promotes</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">proteolytic</tok> <tok cat="NN">degradation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IkappaBalpha</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="NN">IkappaBbeta</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">resulting</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">increase</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nucleus</tok></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="PP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">RAW</tok> <tok cat="CD">264.7</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1038339708@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">reduction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IkappaBalpha</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">DZA</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP" syn="COOD"><tok cat="CC">neither</tok> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">IkappaB</tok> <tok cat="NN">kinase</tok> <tok cat="NN">complex</tok> <tok cat="NN">activation</tok></cons></cons></cons> <tok cat="CC">nor</tok> <cons cat="VP"><tok cat="VBN">modulated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">homocysteine</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1038339709@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">study</tok></cons> <cons cat="ADVP"><tok cat="RB">strongly</tok></cons> <cons cat="VP"><tok cat="VBZ">suggests</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">DZA</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">potent</tok> <tok cat="NN">drug</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">treatment</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">diseases</tok></cons></cons></cons> <cons cat="SBAR"><cons cat="WHPP" id="i5"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NF-kappaB</tok></cons> <cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">central</tok> <tok cat="JJ">pathogenic</tok> <tok cat="NN">role</tok></cons><tok cat="COMMA">,</tok> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">useful</tok> <tok cat="NN">tool</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">studying</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">regulation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">physiological</tok> <tok cat="NNS">functions</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons></cons></cons></cons></cons><cons cat="PP" ref="i5" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1038394001@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">STAT1</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="NN">monocyte</tok> <tok cat="TO">to</tok> <tok cat="NN">macrophage</tok> <tok cat="NN">maturation</tok></cons></cons></cons><tok cat="COLON">:</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">adhesion</tok> <tok cat="NNS">molecules</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1038394002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Human</tok> <tok cat="NNS">monocytes</tok></cons> <cons cat="VP"><tok cat="VBN">isolated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">healthy</tok> <tok cat="NNS">donors</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">time-dependent</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="NNS">macrophages</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">upon</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons> <tok cat="NN">cultivation</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">closely</tok></cons> <cons cat="VP"><tok cat="VBG">mimicking</tok> <cons cat="NP" syn="COOD"><tok cat="PRPP">their</tok> <cons cat="NP"><tok cat="FW">in</tok> <tok cat="FW">vivo</tok> <tok cat="NN">migration</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">maturation</tok></cons></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="JJ">extravascular</tok> <tok cat="NNS">tissues</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1038394003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">mediator</tok><cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">s</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">maturation</tok> <tok cat="NN">process</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="ADVP"><tok cat="RB">yet</tok></cons> <cons cat="VP"><tok cat="VBN">defined</tok><cons cat="NP" ref="i1" null="NONE"></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1038394004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">investigated</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">involvement</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">signal</tok> <tok cat="NNS">transducers</tok> <tok cat="CC">and</tok> <tok cat="NNS">activators</tok> <tok cat="IN">of</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">STAT</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NNS">factors</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">phenomenon</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">reported</tok> <cons cat="NP"><cons cat="NP" id="i2"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">specific</tok></cons><tok cat="COMMA">,</tok> <cons cat="ADJP"><tok cat="JJ">time-dependent</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT1</tok> <tok cat="NN">protein</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" id="i3" role="SBJ" null="NONE"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBG">starting</tok> <cons cat="PP" adv="TMP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">day</tok> <cons cat="QP"><tok cat="CD">0/1</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cultivation</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">maximally</tok></cons> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP" adv="TMP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="NN">day</tok> <tok cat="CD">5</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@42@@oe@16-12-2010 1038394005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">STAT1</tok> <tok cat="NN">activity</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">evident</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">STAT</tok> <tok cat="NN">binding</tok> <tok cat="NNS">sequences</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">SBE</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="ADJP"><tok cat="JJ">present</tok> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">promoters</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">genes</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i14"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i14" id="i15" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">up-regulated</tok> <cons cat="NP" ref="i15" null="NONE"></cons><cons cat="PP"><tok cat="IN">during</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">monocyte</tok></cons> <tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">macrophage</tok></cons></cons> <tok cat="NN">maturation</tok></cons></cons> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">FcgammaRI</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">ICAM-1</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">promoter</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">IFN</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">factor-1</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1038394006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">adhesion</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">fibronectin</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">laminin</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">studied</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">investigate</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">mechanisms</tok></cons> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">STAT1</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1038394007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" ref="i6" id="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">Compared</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">monocytes</tok></cons> <cons cat="ADJP"><tok cat="JJ">adherent</tok> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">plastic</tok> <tok cat="NNS">surfaces</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i6" role="SBJ"><cons cat="NP" id="i7"><cons cat="ADJP"><tok cat="RB">freshly</tok> <tok cat="VBN">isolated</tok></cons> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">allowed</tok> <cons cat="NP" null="NONE"></cons><cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">adhere</tok> <cons cat="PP"><cons cat="ADVP"><tok cat="CC">either</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">fibronectin-</tok> <cons cat="NP" ref="i8" null="QSTN"></cons></cons><tok cat="CC">or</tok> <cons cat="NP" id="i8"><tok cat="JJ">laminin-coated</tok> <tok cat="NNS">flasks</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">exhibited</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="VBN">increased</tok> <tok cat="NN">STAT1</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP" syn="COOD"><tok cat="CC">both</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">control</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">IFN-gamma-treated</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1038394008@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" id="i9"><tok cat="DT">The</tok> <tok cat="JJ">molecular</tok> <tok cat="NNS">events</tok></cons> <cons cat="VP"><tok cat="VBG">leading</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><tok cat="VBN">enhanced</tok> <cons cat="NP"><tok cat="NN">STAT1</tok> <tok cat="NN">activation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NN">responsiveness</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">concerned</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NN">Y701</tok> <cons cat="NP" ref="i16" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">S727</tok> <cons cat="NP" ref="i16" null="RNR"></cons></cons><cons cat="NP" id="i16"><tok cat="NN">STAT1</tok> <tok cat="NN">phosphorylation</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1038394009@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Exogenous</tok> <tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBG">transforming</tok> <tok cat="NN">growth</tok> <tok cat="NN">factor-beta</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i10"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i10" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">exerts</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">inhibitory</tok> <tok cat="NN">effect</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="JJ">monocytic</tok> <tok cat="NN">differentiation</tok> <tok cat="NNS">markers</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">macrophage</tok> <tok cat="NN">maturation</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">integrin</tok> <tok cat="NN">expression</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">STAT1</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1038394010@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" ref="i12" id="i11" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">Taken</tok> <cons cat="NP" ref="i11" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">together</tok></cons></cons></cons> <cons cat="NP" id="i12" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i13" role="SBJ"><tok cat="NN">STAT1</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">plays</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">pivotal</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">differentiation/maturation</tok> <tok cat="NN">process</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">early</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">initially</tok></cons> <tok cat="VBN">activated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">adherence</tok></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="ADVP"><tok cat="RB">then</tok></cons> <cons cat="VP"><cons cat="ADJP" role="PRD"><tok cat="JJ">able</tok> <cons cat="S"><cons cat="NP" ref="i13" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">modulate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">functional</tok> <tok cat="NNS">genes</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">ICAM-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">FcgammaRI</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1038409401@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Cutting</tok> <tok cat="NN">edge</tok><tok cat="COLON">:</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF</tok> <tok cat="IN">of</tok> <tok cat="VBN">activated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">eosinophils</tok></cons></cons><tok cat="COLON">:</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="NN">regulation</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-4</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-5</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1038409402@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">report</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" syn="COOD" id="i1" role="SBJ"><cons cat="NP"><tok cat="NN">NF-AT1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">NF-AT4</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">expressed</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">cytoplasmically</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="NNS">eosinophils</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i2" role="SBJ"><cons cat="NP"><tok cat="NN">NF-AT2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">NF-AT3</tok></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">seen</tok><cons cat="NP" ref="i2" null="NONE"></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1038409403@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="ADVP"><tok cat="RB">Likewise</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" syn="COOD" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">NF-AT1</tok> <tok cat="NN">mRNA</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">NF-AT4</tok> <tok cat="NN">mRNA</tok></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="NNS">eosinophils</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="PRPP">their</tok> <tok cat="NNS">levels</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBN">up-regulated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">Th2-associated</tok> <tok cat="NNS">cytokines</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-4</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-5</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@29@@oe@16-12-2010 1038409404@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="EX">There</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP"><tok cat="DT">no</tok> <tok cat="JJ">detectable</tok> <tok cat="NN">NF-AT</tok> <tok cat="NN">protein</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">nuclei</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="NNS">eosinophils</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1038409405@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons> <cons cat="NP" role="SBJ"><tok cat="NNS">NF-ATs</tok></cons> <cons cat="VP"><tok cat="VBP">appear</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">nuclei</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-4-</tok><cons cat="NP" null="QSTN"></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IL-5-</tok><cons cat="NP" null="QSTN"></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">ionomycin-stimulated</tok> <tok cat="NNS">eosinophils</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1038409406@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><tok cat="RB">Only</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NF-AT1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">NF-AT4</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-AT2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">NF-AT3</tok></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">translocated</tok> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">nuclei</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-4-</tok> <cons cat="NP" null="QSTN"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">IL-5-stimulated</tok> <tok cat="NNS">eosinophils</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1038409407@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">delineate</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="NN">pathway</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cytokine</tok> <tok cat="NN">network</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i7"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Th2</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="VP"><tok cat="LQT">"</tok><tok cat="VBP">control</tok><tok cat="RQT">"</tok> <cons cat="NP"><tok cat="NNS">eosinophils</tok></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">release</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IL-4</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">IL-5</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-AT</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">eosinophils</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1038409408@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NNS">findings</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">a</tok> <tok cat="JJR">later</tok> <tok cat="NN">feedback</tok> <tok cat="LQT">"</tok><tok cat="NN">talking</tok><tok cat="RQT">"</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">exist</tok> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">eosinophils</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">Th2</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1038415301@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Altered</tok> <tok cat="NN">memory</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">early</tok> <tok cat="JJ">rheumatoid</tok> <tok cat="NN">arthritis</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1038415302@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">chronic</tok> <tok cat="JJ">immune</tok> <tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">rheumatoid</tok> <tok cat="NN">arthritis</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">RA</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="MD">might</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">driven</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="VBN">activated</tok> <tok cat="NN">Th1</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="NP"><tok cat="JJ">sufficient</tok> <tok cat="NN">Th2</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">down-modulate</tok> <cons cat="NP"><tok cat="NN">inflammation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1038415303@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">test</tok> <cons cat="SBAR"><tok cat="IN">whether</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="VBN">disordered</tok> <tok cat="NN">memory</tok> <tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="VP"><tok cat="VBZ">contributes</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">typical</tok> <tok cat="JJ">Th1-dominated</tok> <tok cat="JJ">chronic</tok> <tok cat="NN">inflammation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">RA</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="NP" id="i2" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">investigated</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="JJ">CD4+</tok> <tok cat="NN">memory</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="JJ">early</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><cons cat="NP"><tok cat="CD">6</tok> <tok cat="NN">wk</tok></cons> <tok cat="TO">to</tok> <cons cat="NP"><tok cat="CD">12</tok> <tok cat="NN">mo</tok></cons></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="JJ">untreated</tok> <tok cat="NN">RA</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="NN">age-</tok> <cons cat="ADJP" null="QSTN"></cons></cons><tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">sex-matched</tok></cons></cons> <tok cat="JJ">healthy</tok> <tok cat="NNS">controls</tok></cons></cons></cons> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@49@@oe@16-12-2010 1038415304@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">No</tok> <tok cat="NN">difference</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cytokine</tok> <tok cat="NN">secretion</tok> <tok cat="NNS">profiles</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="RB">freshly</tok> <tok cat="VBN">isolated</tok> <tok cat="NN">memory</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">controls</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1038415305@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="NN">cell</tok> <tok cat="NN">culture</tok> <tok cat="NN">system</tok></cons> <cons cat="SBAR" ref="i5" null="ICH"></cons></cons><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">then</tok></cons> <cons cat="VP"><tok cat="VBN">employed</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="SBAR" id="i5"><cons cat="WHNP" id="i6"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">permitted</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">Th</tok> <tok cat="NNS">effectors</tok></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="NN">memory</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">short</tok> <tok cat="NN">term</tok> <tok cat="NN">priming</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1038415306@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="JJ">Marked</tok> <tok cat="NNS">differences</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">priming</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@9@@oe@16-12-2010 1038415307@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="NN">Th2</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="MD">could</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">all</tok> <tok cat="JJ">healthy</tok> <tok cat="NNS">controls</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">priming</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">anti-CD28</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TCR</tok> <tok cat="NN">ligation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1038415308@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">By</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="S" role="SBJ"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="NN">priming</tok> <cons cat="PP"><tok cat="IN">under</tok> <cons cat="NP"><tok cat="DT">those</tok> <tok cat="NNS">conditions</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">resulted</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Th2</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="RB">only</tok> <tok cat="CD">9</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="CD">24</tok> <tok cat="NN">RA</tok> <tok cat="NNS">patients</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1038415309@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Exogenous</tok> <tok cat="NN">IL-4</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="MD">could</tok> <cons cat="VP"><tok cat="VB">overcome</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">apparent</tok> <tok cat="NN">Th2</tok> <tok cat="NN">differentiation</tok> <tok cat="NN">defect</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="CD">seven</tok> <tok cat="NNS">patients</tok></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="PP" role="PRD"><tok cat="IN">without</tok> <cons cat="NP"><tok cat="NN">effect</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="VBG">remaining</tok> <tok cat="CD">eight</tok> <tok cat="NNS">patients</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1038415310@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">all</tok> <tok cat="NNS">patients</tok></cons></cons> <cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">marked</tok> <tok cat="NN">decrease</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">IL-2-producing</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">significant</tok> <tok cat="NN">increase</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">well-differentiated</tok> <tok cat="NN">Th1</tok> <tok cat="NNS">cells</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i9"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">produced</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">IFN-gamma</tok></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="NN">IL-2</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">evident</tok> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">priming</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">anti-CD3</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">anti-CD28</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1038415311@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="NP" id="i10" role="SBJ"><cons cat="NP"><tok cat="JJ">CD4+</tok> <tok cat="NN">memory</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">early</tok> <tok cat="JJ">untreated</tok> <tok cat="NN">RA</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">manifest</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">intrinsic</tok> <tok cat="NN">abnormality</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">ability</tok> <cons cat="S"><cons cat="NP" ref="i10" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">differentiate</tok> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">specific</tok> <tok cat="JJ">cytokine-producing</tok> <tok cat="NN">effector</tok> <tok cat="NNS">cells</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i11"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="MD">might</tok> <cons cat="VP"><tok cat="VB">contribute</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">characteristic</tok> <tok cat="JJ">Th1-dominated</tok> <tok cat="JJ">chronic</tok> <tok cat="LRB">(</tok><tok cat="JJ">auto</tok><tok cat="RRB">)</tok><tok cat="JJ">immune</tok> <tok cat="NN">inflammation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">RA</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1038565001@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Functional</tok> <tok cat="NN">B-cell</tok> <tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">intrahepatic</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">follicles</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">C</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@12@@oe@16-12-2010 1038565002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Intrahepatic</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NN">follicle</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">ILF</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">formation</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="CD">one</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="ADJP" syn="COOD"><tok cat="DT">the</tok> <cons cat="ADJP"><tok cat="RBS">most</tok> <tok cat="JJ">characteristic</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="RB">commonly</tok> <tok cat="VBN">observed</tok></cons></cons> <tok cat="JJ">histological</tok> <tok cat="NNS">features</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">C</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1038565003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i1" role="SBJ"><tok cat="JJ">little</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="VBG">regarding</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">whether</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">follicles</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">liver</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">belong</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">functional</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">tissues</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHADVP" id="i2"><tok cat="WRB">where</tok></cons> <cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBN">activated</tok><cons cat="NP" ref="i3" null="NONE"></cons><cons cat="ADVP" ref="i4" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">differentiated</tok><cons cat="NP" ref="i3" null="NONE"></cons><cons cat="ADVP" ref="i4" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBN">proliferated</tok><cons cat="NP" ref="i3" null="NONE"></cons><cons cat="ADVP" ref="i4" null="RNR"></cons></cons><cons cat="ADVP" ref="i2" id="i4" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">or</tok> <cons cat="SBAR"><tok cat="IN">if</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="DT">the</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">merely</tok></cons> <cons cat="VP"><tok cat="VBN">infiltrated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">recruitment</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">secondary</tok> <tok cat="JJ">lymphoid</tok> <tok cat="NNS">organs</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1038565004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">ascertain</tok> <cons cat="VP"><tok cat="DT">this</tok> <tok cat="NN">possibility</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">examined</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">markers</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">B-cell</tok> <tok cat="NN">activation</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">differentiation</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">proliferation</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">ILFs</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">C</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="RB">surgically</tok> <tok cat="JJ">resected</tok></cons> <tok cat="NNS">specimens</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">compared</tok> <cons cat="NP"><tok cat="PRP">them</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">specimens</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">perihepatic</tok> <tok cat="NN">lymph</tok> <tok cat="NNS">nodes</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">immunohistochemical</tok> <tok cat="NN">technique</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@46@@oe@16-12-2010 1038565005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Germinal</tok> <tok cat="NN">center</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">GC</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">formation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">ILFs</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">frequently</tok></cons> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">HCV-positive</tok> <tok cat="NNS">cases</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1038565006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">distribution</tok></cons> <cons cat="NP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">immunoglobulin</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="NN">M</tok> <tok cat="LRB">(</tok><tok cat="NN">IgM</tok><tok cat="RRB">)</tok><tok cat="COLON">-</tok><cons cat="ADJP" null="QSTN"></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADJP"><tok cat="NN">IgD-</tok><cons cat="ADJP" null="QSTN"></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">IgG-positive</tok></cons></cons> <tok cat="NNS">cells</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok> <tok cat="NNS">patterns</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Ki-67</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">CD23</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">or</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">bcl-2</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">bcl-6</tok> <cons cat="NP" ref="i9" null="RNR"></cons></cons><cons cat="NP" id="i9"><tok cat="NN">gene</tok> <tok cat="NNS">products</tok></cons></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">follicles</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">GC</tok> <tok cat="NN">formation</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">liver</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">C</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">similar</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">lymph</tok> <tok cat="NNS">nodes</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">indicating</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i10" role="SBJ"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBN">activated</tok><cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP" ref="i11" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">proliferated</tok><cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP" ref="i11" null="RNR"></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBN">differentiated</tok> <cons cat="NP" ref="i10" null="NONE"></cons><cons cat="PP" ref="i11" null="RNR"></cons></cons><cons cat="PP" id="i11"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">ILFs</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">GC</tok> <tok cat="NN">formation</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">C</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@77@@oe@16-12-2010 1038565007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i12" role="SBJ"><cons cat="NP"><tok cat="JJ">Oligoclonal</tok> <tok cat="NN">expansion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">livers</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NNS">ILFs</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">confirmed</tok> <cons cat="NP" ref="i12" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">immunoglobulin</tok> <tok cat="JJ">heavy</tok> <tok cat="NN">chain</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="JJ">IgH</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NN">gene</tok> <tok cat="NN">rearrangement</tok></cons> <cons cat="VP"><tok cat="VBN">determined</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="NN">polymerase</tok> <tok cat="NN">chain</tok> <tok cat="NN">reaction</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">PCR</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1038565008@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">data</tok></cons> <cons cat="ADVP"><tok cat="RB">strongly</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NNS">ILFs</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">GC</tok> <tok cat="NN">formation</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i13"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i13" id="i14" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADVP"><tok cat="RB">frequently</tok></cons> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i14" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NN">hepatitis</tok> <tok cat="NN">C</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="ADVP"><tok cat="RB">functionally</tok></cons> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">same</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">those</tok></cons> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">lymph</tok> <tok cat="NNS">nodes</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">respect</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">B-cell</tok> <tok cat="NN">expansion</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="NN">maturation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1039520101@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">Ovarian</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">breast</tok></cons></cons> <tok cat="JJ">cytotoxic</tok> <tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">recognize</tok> <cons cat="NP"><tok cat="NNS">peptides</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">amino</tok> <tok cat="NN">enhancer</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">split</tok> <tok cat="NN">protein</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Notch</tok> <tok cat="NN">complex</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1039520102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">investigated</tok> <cons cat="NP"><tok cat="NN">recognition</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">ovarian</tok> <tok cat="NN">tumor</tok> <tok cat="JJ">associated</tok> <tok cat="NN">lymphocyte</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">OVTAL</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">breast</tok> <tok cat="NN">tumor</tok> <tok cat="JJ">associated</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">BRTAL</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">peptides</tok></cons> <cons cat="PP"><tok cat="VBG">corresponding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">sequence</tok> <tok cat="CD">125-135</tok> <tok cat="IN">of</tok> <tok cat="DT">the</tok> <tok cat="NN">Aminoenhancer</tok> <tok cat="IN">of</tok> <tok cat="JJ">split</tok> <tok cat="LRB">(</tok><tok cat="NN">AES</tok><tok cat="RRB">)</tok> <tok cat="NN">protein</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1039520103@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="CD">Three</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">peptides</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBN">designated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">G75:AES1/2</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">128-135</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">G60: AES1/2</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">127-137</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">G61: AES1/2</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">125-133</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">correspond</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">wildtype</tok> <tok cat="NN">AES</tok> <tok cat="NN">sequence</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="JJ">fourth</tok> <tok cat="NN">G76:GPLTPLPV</tok><tok cat="COMMA">,</tok> <tok cat="NN">AES1/2</tok> <tok cat="LRB">(</tok><tok cat="CD">128-135</tok><tok cat="RRB">)</tok></cons> <cons cat="VP"><tok cat="VBZ">corresponds</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">variant</tok> <tok cat="NN">sequence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">peptide</tok> <tok cat="NN">G75</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">N-terminal</tok> <tok cat="NN">Leu</tok></cons> <cons cat="VP"><tok cat="VBN">substituted</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">glycine</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@53@@oe@16-12-2010 1039520104@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">sequences</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">chosen</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">study</tok></cons></cons> <cons cat="SBAR"><tok cat="IN">because</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">mass-spectrometric</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MS</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">CTL</tok> <tok cat="JJ">active</tok> <tok cat="NN">HPLC</tok> <tok cat="NN">peptide</tok> <tok cat="NN">fraction</tok></cons> <cons cat="VP"><tok cat="VBN">eluted</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">immunoaffinity</tok> <tok cat="JJ">precipitated</tok> <tok cat="NN">HLA-A2</tok> <tok cat="NN">molecule</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBD">revealed</tok></cons></cons></cons></cons><tok cat="COLON">:</tok></cons> <cons cat="NP"><cons cat="NP"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">a</tok><tok cat="RRB">)</tok></cons> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">ion</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">mass-to-charge</tok> <tok cat="NN">ratio</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">m/z</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">793</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP"><cons cat="ADJP"><tok cat="RBR">more</tok> <tok cat="JJ">abundant</tok></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="NNS">ions</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">similar</tok> <tok cat="NNS">masses</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok></cons> <cons cat="S"><cons cat="LST"><tok cat="LRB">(</tok><tok cat="LS">b</tok><tok cat="RRB">)</tok></cons> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP"><tok cat="RB">tentatively</tok> <tok cat="VBN">reconstituted</tok></cons> <tok cat="NN">sequence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ion</tok> <tok cat="CD">793</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">matched</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">sequence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">peptide</tok> <tok cat="NN">G76</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@74@@oe@16-12-2010 1039520105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">AES</tok> <tok cat="NNS">peptides</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">G75</tok> <tok cat="LRB">(</tok><tok cat="CD">128-135</tok><tok cat="RRB">)</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">G76</tok> <tok cat="LRB">(</tok><tok cat="CD">128-135</tok><tok cat="RRB">)</tok> <tok cat="LRB">(</tok><tok cat="NN">L128G</tok><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">reconstituted</tok> <cons cat="NP"><tok cat="NN">CTL</tok> <tok cat="NN">recognition</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">concentrations</tok></cons> <cons cat="VP"><tok cat="VBG">ranging</tok> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP"><cons cat="QP"><tok cat="CD">200-500</tok></cons> <tok cat="NN">nM</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1039520106@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">concentrations</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><cons cat="ADJP"><tok cat="JJR">lower</tok></cons> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">concentrations</tok></cons> <cons cat="VP"><tok cat="VBN">reported</tok> <cons cat="NP" id="i3" null="NONE"></cons><cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">effector</tok> <tok cat="NN">function</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CTL</tok> <tok cat="VBG">recognizing</tok> <tok cat="JJ">other</tok> <tok cat="JJ">epithelial</tok> <tok cat="NN">tumor</tok> <tok cat="NN">Ag</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1039520107@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Furthermore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="VBN">cloned</tok> <tok cat="JJ">CD8+</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">indicated</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">G75</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">G76</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <tok cat="RB">not</tok> <cons cat="NP" role="PRD"><tok cat="JJ">cross-reactive</tok> <tok cat="NNS">specificities</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">suggesting</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">key</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">N-terminal</tok> <tok cat="NNS">residues</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">variant</tok> <tok cat="NN">peptide</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">dictating</tok> <cons cat="NP"><tok cat="NNS">specificities</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1039520108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" syn="COOD"><cons cat="SBAR" func="ADV"><tok cat="IN">Since</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">AES</tok> <tok cat="NNS">proteins</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="NN">part</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">set</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NNS">repressors</tok></cons> <cons cat="VP"><tok cat="VBN">encoded</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">the</tok> <tok cat="NN">Enhancer</tok> <tok cat="IN">of</tok> <tok cat="JJ">split</tok> <tok cat="LRB">[</tok><tok cat="NN">E(spl)</tok><tok cat="RRB">]</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <tok cat="CC">and</tok> <cons cat="SBAR" func="ADV"><tok cat="IN">since</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">repressors</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">suppress</tok> <cons cat="NP"><tok cat="NN">cell</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">Notch</tok> <tok cat="NNS">receptors</tok> <tok cat="NN">signalling</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons></cons> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">AES</tok> <tok cat="NNS">peptides</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">represent</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">novel</tok> <tok cat="NN">class</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">self-antigens</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i5"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">deserve</tok> <cons cat="NP"><tok cat="JJ">further</tok> <tok cat="NN">consideration</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">Ag</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">epithelial</tok> <tok cat="NNS">cancers</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@61@@oe@16-12-2010 1039564501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">activity</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><tok cat="JJ">caspase-dependent</tok> <tok cat="NN">apoptosis</tok></cons> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">detectable</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">caspase-1</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP" null="QSTN"></cons><tok cat="CD">-3</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1039564502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">involved</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">transcriptional</tok> <tok cat="NN">control</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">various</tok> <tok cat="NNS">genes</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">act</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">extrinsic</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">intrinsic</tok></cons></cons> <tok cat="NN">survival</tok> <tok cat="NNS">factors</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1039564503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">suppression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">activity</tok></cons></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cell-permeable</tok> <tok cat="NN">SN50</tok> <tok cat="NN">peptide</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i3"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">masks</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">localization</tok> <tok cat="NN">sequence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B1</tok> <tok cat="NNS">dimers</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">prevents</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">localization</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBZ">induces</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="JJ">normal</tok> <tok cat="JJ">human</tok> <tok cat="NN">PBL</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1039564504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">resulted</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">externalization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">phosphatidylserine</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NNS">breaks</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">morphological</tok> <tok cat="NNS">changes</tok></cons> <cons cat="ADJP"><tok cat="JJ">consistent</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1039564505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="NN">DNA</tok> <tok cat="NN">fragmentation</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><cons cat="ADVP"><tok cat="RB">efficiently</tok></cons> <tok cat="VBN">blocked</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="DT">the</tok> <tok cat="NN">caspase</tok> <tok cat="NN">inhibitor</tok> <tok cat="NN">Z-VAD-fmk</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">partially</tok></cons> <tok cat="VBN">blocked</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">Ac-DEVD-fmk</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">suggesting</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">SN50-mediated</tok> <tok cat="NN">apoptosis</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">caspase-dependent</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1039564506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Interestingly</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="NN">apoptosis</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">suppression</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">contrast</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">that</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><cons cat="NP"><tok cat="NN">TPEN</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="JJ">N,N,N',N'-tetrakis</tok> <tok cat="NN">[2-pyridylmethyl]ethylenediamine</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">soluble</tok> <tok cat="NN">Fas</tok> <tok cat="NN">ligand</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">CD95</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">active</tok> <tok cat="NN">death</tok> <tok cat="NN">effector</tok> <tok cat="NNS">proteases</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">caspase-1-like</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-1</tok> <tok cat="NN">converting</tok> <tok cat="NN">enzyme</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">caspase-3-like</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">CPP32/Yama/apopain</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">caspase-6-like</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">without</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cleavage</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">caspase-3</tok> <tok cat="NNS">substrates</tok></cons> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">poly(ADP-ribose)</tok> <tok cat="NN">polymerase</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">DNA</tok> <tok cat="NN">fragmentation</tok> <tok cat="NN">factor-45</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@65@@oe@16-12-2010 1039564507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR" syn="COOD"><tok cat="CC">either</tok> <cons cat="SBAR"><cons cat="COMP" null="ZERO"></cons><cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="JJ">low</tok> <tok cat="NN">level</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">activation</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i6" null="NONE"></cons></cons></cons></cons></cons><tok cat="CC">or</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><tok cat="JJ">different</tok> <tok cat="NNS">caspases</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">involved</tok><cons cat="NP" ref="i7" null="NONE"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1039564508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Preactivation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBG">resulting</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">protected</tok> <cons cat="NP"><tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">SN50-induced</tok> <tok cat="NN">apoptosis</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1039564509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">demonstrate</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">essential</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">survival</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">naive</tok> <tok cat="NN">PBL</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1039565201@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Signaling</tok> <tok cat="NNS">events</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="JJ">lipopolysaccharide-activated</tok> <tok cat="JJ">toll-like</tok> <tok cat="NN">receptor</tok> <tok cat="CD">2</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@9@@oe@16-12-2010 1039565202@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="JJ">Human</tok> <tok cat="JJ">Toll-like</tok> <tok cat="NN">receptor</tok> <tok cat="CD">2</tok> <tok cat="LRB">(</tok><tok cat="NN">TLR2</tok><tok cat="RRB">)</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">signaling</tok> <tok cat="NN">receptor</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">responds</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">LPS</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">activates</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1039565203@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Here</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">investigate</tok> <cons cat="ADVP"><tok cat="RBR">further</tok></cons> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">events</tok></cons> <cons cat="VP"><tok cat="VBN">triggered</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">TLR2</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">response</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">LPS</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1039565204@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NN">TLR2</tok></cons> <cons cat="VP"><tok cat="NNS">associates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">high-affinity</tok> <tok cat="NN">LPS</tok> <tok cat="NN">binding</tok> <tok cat="NN">protein</tok> <tok cat="NN">membrane</tok> <tok cat="NN">CD14</tok></cons></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">serve</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">LPS</tok> <tok cat="NN">receptor</tok> <tok cat="NN">complex</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">LPS</tok> <tok cat="NN">treatment</tok></cons> <cons cat="VP"><tok cat="VBZ">enhances</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">oligomerization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TLR2</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1039565205@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="JJ">Concomitant</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">receptor</tok> <tok cat="NN">oligomerization</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i3" role="SBJ"><tok cat="DT">the</tok> <tok cat="JJ">IL-1R-associated</tok> <tok cat="NN">kinase</tok> <tok cat="LRB">(</tok><tok cat="NN">IRAK</tok><tok cat="RRB">)</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">recruited</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">TLR2</tok> <tok cat="NN">complex</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1039565206@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Intracellular</tok> <tok cat="NN">deletion</tok> <tok cat="NNS">variants</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">TLR2</tok></cons> <cons cat="VP"><tok cat="VBG">lacking</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">C-terminal</tok> <tok cat="CD">13</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="CD">141</tok> <tok cat="NN">aa</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">fail</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">recruit</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IRAK</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">consistent</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">inability</tok></cons> <cons cat="S" ref="i5" null="ICH"></cons></cons><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">mutants</tok></cons></cons> <cons cat="S" id="i5"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">transmit</tok> <cons cat="NP"><tok cat="NN">LPS</tok> <tok cat="JJ">cellular</tok> <tok cat="NN">signaling</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1039565207@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Moreover</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">both</tok> <tok cat="NN">deletion</tok> <tok cat="NNS">mutants</tok></cons> <cons cat="VP"><tok cat="MD">could</tok> <cons cat="ADVP"><tok cat="RB">still</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">form</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">complexes</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">wild-type</tok> <tok cat="NN">TLR2</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VB">act</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dominant-negative</tok> <tok cat="LRB">(</tok><tok cat="JJ">DN</tok><tok cat="RRB">)</tok> <tok cat="NN">fashion</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">block</tok> <cons cat="NP"><tok cat="JJ">TLR2-mediated</tok> <tok cat="NN">signal</tok> <tok cat="NN">transduction</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1039565208@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">DN</tok> <tok cat="NNS">constructs</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">myeloid</tok> <tok cat="NN">differentiation</tok> <tok cat="NN">protein</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">IRAK</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">TNF</tok> <tok cat="JJ">receptor-associated</tok> <tok cat="NN">factor</tok> <tok cat="CD">6</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">NF-kappaB-inducing</tok> <tok cat="NN">kinase</tok></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i6"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" id="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">coexpressed</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">TLR2</tok></cons></cons><cons cat="ADVP" ref="i6" null="T"></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBP">abrogate</tok> <cons cat="NP"><tok cat="JJ">TLR2-mediated</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1039565209@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBP">reveal</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="VBN">conserved</tok> <tok cat="NN">signaling</tok> <tok cat="NN">pathway</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">TLR2</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">IL-1Rs</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">mechanism</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TLR2</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="JJ">DN</tok> <tok cat="NNS">variants</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1039567101@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Janus</tok> <tok cat="NN">kinase</tok> <tok cat="NN">3-STAT5a</tok> <tok cat="NN">pathway</tok></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">after</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD40</tok> <tok cat="NN">triggering</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">monocytes</tok></cons></cons> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1039567102@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">CD40/CD40</tok> <tok cat="NN">ligand</tok> <tok cat="NNS">interactions</tok></cons> <cons cat="VP"><tok cat="VBP">play</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">key</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">immune</tok> <tok cat="NNS">responses</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">lymphocytes</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">dendritic</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1039567103@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">signal</tok> <tok cat="NN">transduction</tok> <tok cat="NNS">events</tok></cons> <cons cat="VP"><tok cat="VBN">triggered</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">cross-linking</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">CD40</tok> <tok cat="NN">receptor</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="ADVP"><tok cat="RB">widely</tok></cons> <cons cat="VP"><tok cat="VBN">studied</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="JJ">little</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">known</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">about</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">signaling</tok></cons> <cons cat="PP"><tok cat="VBG">following</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD40</tok> <tok cat="NN">stimulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">monocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="JJ">tonsillar</tok> <tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1039567104@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Therefore</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">studied</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">CD40</tok> <tok cat="NN">pathway</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="ADJP"><tok cat="RB">highly</tok> <tok cat="VBN">purified</tok></cons> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NNS">monocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1039567105@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP" adv="TMP"><tok cat="IN">After</tok> <cons cat="NP"><tok cat="NN">CD40</tok> <tok cat="NN">triggering</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">similar</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP" id="i3"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappaB</tok> <cons cat="PRN"><tok cat="LRB">(</tok><tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons map="i3" cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">AP-1</tok></cons></cons><tok cat="RRB">)</tok></cons> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">complex</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">occurred</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">both</tok> <tok cat="NN">cell</tok> <tok cat="NNS">preparations</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1039567106@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">components</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NNS">complexes</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">different</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">monocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">because</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">p50</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="NN">part</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">complex</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">CD40</tok> <tok cat="NN">triggering</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="NN">p65</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">only</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@44@@oe@16-12-2010 1039567107@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">contrast</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR" func="ADV"><tok cat="IN">although</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">Janus</tok> <tok cat="NN">kinase</tok> <tok cat="CD">3</tok> <tok cat="NN">tyrosine</tok> <tok cat="NN">kinase</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">CD40</tok> <tok cat="NNS">molecules</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="VBG">resting</tok> <tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i6" role="SBJ"><tok cat="NN">Janus</tok> <tok cat="NN">kinase</tok> <tok cat="CD">3</tok> <tok cat="NN">phosphorylation</tok> <tok cat="NN">induction</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><cons cat="ADVP"><tok cat="RB">only</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">CD40-activated</tok> <tok cat="NNS">monocytes</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">subsequent</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">STAT5a</tok> <tok cat="NN">DNA</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">nucleus</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@47@@oe@16-12-2010 1039567108@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok> <tok cat="NNS">signals</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">B</tok> <tok cat="NNS">cells</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">differ</tok> <cons cat="PP"><tok cat="VBG">following</tok> <cons cat="NP"><tok cat="NN">CD40</tok> <tok cat="NN">stimulation</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1039567109@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">observation</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">consistent</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">detection</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">CD40-induced</tok> <tok cat="NN">monocyte</tok> <tok cat="NN">activation</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">CD40</tok> <tok cat="JJ">ligand+</tok> <tok cat="NN">hyper</tok> <tok cat="NN">IgM</tok> <tok cat="NN">syndrome</tok></cons></cons></cons> <cons cat="SBAR"><cons cat="WHPP" id="i7"><tok cat="IN">in</tok> <cons cat="WHNP"><tok cat="WP">whom</tok></cons></cons> <cons cat="S"><cons cat="NP" id="i8" role="SBJ"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">defect</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">CD40-induced</tok> <tok cat="NN">B</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">reported</tok><cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP" ref="i7" null="T"></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1039629001@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Clonality</tok> <tok cat="NN">analysis</tok></cons> <cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="NN">X-chromosome</tok> <tok cat="NN">inactivation</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">androgen</tok> <tok cat="NN">receptor</tok> <tok cat="NN">gene</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">Humara</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1039629002@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Evaluation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">large</tok> <tok cat="NNS">cohorts</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="JJ">myeloproliferative</tok> <tok cat="NNS">diseases</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">secondary</tok> <tok cat="NN">neutrophilia</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">reactive</tok> <tok cat="NN">thrombocytosis</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1039629003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="JJ">Chronic</tok> <tok cat="JJ">myeloproliferative</tok> <tok cat="NNS">diseases</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">MPDs</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><tok cat="JJ">consistent</tok> <cons cat="NP"><tok cat="JJ">cytogenetic</tok> <cons cat="NP" ref="i2" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">molecular</tok> <cons cat="NP" ref="i2" null="RNR"></cons></cons><cons cat="NP" id="i2"><tok cat="NNS">abnormalities</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1039629004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">Demonstration</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">clonal</tok> <tok cat="NN">cell</tok> <tok cat="NN">growth</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">X-chromosome</tok> <tok cat="NN">inactivation</tok> <tok cat="LRB">(</tok><tok cat="NN">XCI</tok><tok cat="RRB">)</tok> <tok cat="NNS">patterns</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">females</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">provides</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">promising</tok> <tok cat="NN">tool</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">diagnosis</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1039629005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i3" role="SBJ"><tok cat="DT">this</tok> <tok cat="NN">technique</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">complicated</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">excessive</tok> <tok cat="NN">lyonization</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBG">mimicking</tok> <cons cat="NP"><tok cat="JJ">clonal</tok> <tok cat="NN">cell</tok> <tok cat="NN">growth</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">analyzed</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">XCI</tok> <tok cat="NNS">patterns</tok></cons> <cons cat="PP"><tok cat="IN">at</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">human</tok> <tok cat="NN">androgen</tok> <tok cat="NN">receptor</tok> <tok cat="LRB">(</tok><tok cat="NN">HUMARA</tok><tok cat="RRB">)</tok> <tok cat="NN">locus</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">146</tok> <tok cat="JJ">healthy</tok> <tok cat="NNS">females</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">65</tok> <tok cat="NNS">women</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">secondary</tok> <tok cat="NN">neutrophilia</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">31</tok> <tok cat="NNS">women</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">reactive</tok> <tok cat="NN">thrombocytosis</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">86</tok> <tok cat="NNS">women</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">chronic</tok> <tok cat="NNS">MPDs</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@55@@oe@16-12-2010 1039629006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="JJ">skewed</tok> <tok cat="NN">XCI</tok> <tok cat="NN">pattern</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><cons cat="QP"><tok cat="JJR">greater</tok> <tok cat="IN">than</tok> <tok cat="CD">75</tok></cons><tok cat="NN">%</tok> <tok cat="NN">amplification</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="CD">1</tok> <tok cat="NN">allele</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">allele</tok> <tok cat="NN">ratio</tok></cons> <cons cat="VP"><tok cat="JJR">></tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">3</tok></cons><tok cat="COLON">:</tok><cons cat="NP"><tok cat="CD">1</tok></cons></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">found</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">22</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">9.1</tok><tok cat="NN">%</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="CD">242</tok> <tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1039629007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">incidence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">skewing</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">statistically</tok></cons> <cons cat="ADJP" role="PRD"><tok cat="RB">significantly</tok> <tok cat="JJR">lower</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">women</tok></cons> <cons cat="ADJP"><tok cat="JJR">younger</tok> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><tok cat="CD">30</tok> <tok cat="NNS">years</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">2/73</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="VBN">compared</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">women</tok></cons> <cons cat="ADJP"><tok cat="JJR">older</tok> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><tok cat="CD">60</tok> <tok cat="NNS">years</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">10/53</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1039629008@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="PP" tpc="TPC" id="i5"><tok cat="IN">Of</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">86</tok> <tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">chronic</tok> <tok cat="NN">MPD</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="CD">71</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">82</tok><tok cat="NN">%</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP" ref="i5" null="T"></cons></cons><cons cat="VP"><tok cat="VBD">exhibited</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">allele</tok> <tok cat="NN">ratio</tok></cons> <cons cat="ADJP"><tok cat="JJR">greater</tok> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">3</tok></cons><tok cat="COLON">:</tok><cons cat="NP"><tok cat="CD">1</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <tok cat="IN">whereas</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="RB">only</tok> <tok cat="CD">10</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="CD">12</tok><tok cat="NN">%</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="CD">86</tok> <tok cat="JJ">age-matched</tok> <tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">skewed</tok> <tok cat="NN">XCI</tok> <tok cat="NN">pattern</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1039629009@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" func="ADV"><tok cat="IN">Although</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">statistical</tok> <tok cat="NN">evaluation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">data</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">significant</tok> <tok cat="NN">difference</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">chronic</tok> <tok cat="NN">MPD</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">control</tok> <tok cat="NNS">subjects</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">proof</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">clonality</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="ADJP"><cons cat="ADJP"><tok cat="NN">individual</tok></cons><tok cat="COMMA">,</tok> <cons cat="ADJP"><tok cat="RB">especially</tok> <tok cat="JJ">elderly</tok></cons><tok cat="COMMA">,</tok></cons> <tok cat="NNS">patients</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">difficult</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1039772201@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">glucocorticoid</tok> <tok cat="NN">receptor</tok></cons> <cons cat="VP"><tok cat="VBZ">cooperates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">erythropoietin</tok> <tok cat="NN">receptor</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">c-Kit</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">enhance</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="VP"><tok cat="VB">sustain</tok> <cons cat="NP" ref="i1" null="RNR"></cons></cons><cons cat="NP" id="i1"><cons cat="NP"><tok cat="NN">proliferation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">progenitors</tok></cons></cons></cons> <cons cat="ADVP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1039772202@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" func="ADV"><tok cat="IN">Although</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">erythropoietin</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">Epo</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">essential</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">mature</tok> <tok cat="JJ">red</tok> <tok cat="NN">blood</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">cooperation</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">other</tok> <tok cat="NNS">factors</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">required</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">proper</tok> <tok cat="NN">balance</tok></cons> <cons cat="PP"><tok cat="IN">between</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">progenitor</tok> <tok cat="NN">proliferation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">differentiation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1039772203@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="JJ">avian</tok> <tok cat="JJ">erythroid</tok> <tok cat="NNS">progenitors</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">steroid</tok> <tok cat="NNS">hormones</tok></cons> <cons cat="VP"><tok cat="VBP">cooperate</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">tyrosine</tok> <tok cat="NN">kinase</tok> <tok cat="NNS">receptors</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">renewal</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">progenitors</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1039772204@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">examined</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">corticosteroids</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vitro</tok></cons> <tok cat="NN">expansion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">primary</tok> <tok cat="JJ">human</tok> <tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">liquid</tok> <tok cat="NNS">cultures</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">colony</tok> <tok cat="NNS">assays</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@23@@oe@16-12-2010 1039772205@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="NN">Dexamethasone</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">Dex</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">synthetic</tok> <tok cat="NN">glucocorticoid</tok> <tok cat="NN">hormone</tok></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBD">cooperated</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">Epo</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">stem</tok> <tok cat="NN">cell</tok> <tok cat="NN">factor</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">progenitors</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i3" null="ZERO"></cons><cons cat="S"><cons cat="NP" ref="i3" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">undergo</tok> <cons cat="NP"><cons cat="QP"><tok cat="CD">15</tok> <tok cat="TO">to</tok> <tok cat="CD">22</tok></cons> <tok cat="NN">cell</tok> <tok cat="NNS">divisions</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">corresponding</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="CD">10(5)-</tok> <tok cat="TO">to</tok> <tok cat="JJ">10(6)-fold</tok> <tok cat="NN">amplification</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1039772206@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">Dex</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">acted</tok> <cons cat="ADVP"><tok cat="RB">directly</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">progenitors</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">maintained</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">colony-forming</tok> <tok cat="NN">capacity</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">progenitor</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">expanded</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">liquid</tok> <tok cat="NNS">cultures</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1039772207@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="NN">hormone</tok></cons> <cons cat="VP"><tok cat="VBD">delayed</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">terminal</tok> <tok cat="NN">differentiation</tok></cons> <cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">erythrocytes</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" id="i5" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">assayed</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">morphology</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">hemoglobin</tok> <tok cat="NN">accumulation</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">genes</tok></cons> <cons cat="ADJP"><tok cat="JJ">characteristic</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">immature</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1039772208@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="JJ">Sustained</tok> <tok cat="NN">proliferation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">erythroid</tok> <tok cat="NNS">progenitors</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">could</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">equally</tok> <tok cat="RB">well</tok></cons> <cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="VBN">purified</tok> <tok cat="JJ">erythroid</tok> <tok cat="JJ">burst-forming</tok> <tok cat="NNS">units</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">BFU-E</tok></cons><tok cat="RRB">)</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">CD34(+)</tok> <tok cat="NN">blast</tok> <tok cat="NNS">cells</tok></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">bone</tok> <tok cat="NN">marrow</tok></cons> <cons cat="VP"><tok cat="VBN">depleted</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">CD34(+)</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010 1040075501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="NN">Escape</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="NN">cytomegalovirus</tok></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">HLA-DR-restricted</tok> <tok cat="JJ">CD4(+)</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">response</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">mediated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">repression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">gamma</tok> <tok cat="JJ">interferon-induced</tok> <tok cat="NN">class</tok> <tok cat="CD">II</tok> <tok cat="NN">transactivator</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1040075502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Human</tok> <tok cat="NN">cytomegalovirus</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">HCMV</tok></cons><tok cat="RRB">)</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">betaherpesvirus</tok></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">pathogen</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i2"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">escapes</tok> <cons cat="NP"><tok cat="JJ">immune</tok> <tok cat="NN">recognition</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="JJ">various</tok> <tok cat="NNS">mechanisms</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1040075503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">paper</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">HCMV</tok></cons> <cons cat="VP"><tok cat="RB">down</tok> <tok cat="VBZ">regulates</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">gamma</tok> <tok cat="NN">interferon</tok> <tok cat="LRB">(</tok><tok cat="NN">IFN-gamma</tok><tok cat="RRB">)</tok><tok cat="JJ">-induced</tok> <tok cat="NN">HLA-DR</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">U373</tok> <tok cat="NN">MG</tok> <tok cat="NN">astrocytoma</tok> <tok cat="NNS">cells</tok></cons></cons></cons> <cons cat="PP"><tok cat="JJ">due</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">defect</tok></cons> <cons cat="ADJP"><tok cat="RB">downstream</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">STAT1</tok> <tok cat="NN">phosphorylation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@35@@oe@16-12-2010 1040075504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">Repression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">class</tok> <tok cat="CD">II</tok> <tok cat="NN">transactivator</tok> <tok cat="LRB">(</tok><tok cat="NN">CIITA</tok><tok cat="RRB">)</tok> <tok cat="NN">mRNA</tok> <tok cat="NN">expression</tok></cons></cons></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">within</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">first</tok> <tok cat="NNS">hours</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IFN-gamma-HCMV</tok> <tok cat="NN">coincubation</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">results</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">HLA-DR</tok> <tok cat="NN">synthesis</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1040075505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">defect</tok></cons> <cons cat="VP"><tok cat="VBZ">leads</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">absence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">presentation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">major</tok> <tok cat="JJ">immediate-early</tok> <tok cat="NN">protein</tok> <tok cat="NN">IE1</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">specific</tok> <tok cat="JJ">CD4(+)</tok> <tok cat="NN">T-cell</tok> <tok cat="NNS">clones</tok></cons></cons></cons></cons></cons></cons> <cons cat="SBAR" adv="TMP"><tok cat="WRB">when</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="NN">U373</tok> <tok cat="NN">MG</tok> <tok cat="NNS">cells</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="JJ">antigen-presenting</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">treated</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">IFN-gamma</tok></cons> <tok cat="CC">plus</tok> <cons cat="NP"><tok cat="NN">HCMV</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1040075506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="NN">presentation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="RB">endogenously</tok> <tok cat="VBN">synthesized</tok> <tok cat="NN">IE1</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">restored</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="SBAR" adv="TMP"><tok cat="WRB">when</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="NN">U373</tok> <tok cat="NN">MG</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="VP"><tok cat="VBN">transfected</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">CIITA</tok></cons></cons> <cons cat="PP" adv="TMP"><tok cat="RB">prior</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">infection</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">HCMV</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1040075507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Altogether</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">defect</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">HCMV</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">resides</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">IFN-gamma-responsive</tok> <tok cat="NN">promoter</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CIITA</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1040075508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">first</tok> <tok cat="NN">demonstration</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">viral</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CIITA</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1040217301@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Suppression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">supernatant</tok> <tok cat="NN">fluid</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">renal</tok> <tok cat="NN">cell</tok> <tok cat="NNS">carcinomas</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1040217302@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">renal</tok> <tok cat="NN">cell</tok> <tok cat="NN">carcinoma</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">RCC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="VBN">reduced</tok> <tok cat="JJ">immune</tok> <tok cat="NN">function</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">impaired</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1040217303@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">determined</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">mechanism</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">suppression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">RCC</tok> <tok cat="NN">patient</tok></cons></cons></cons></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">determined</tok> <cons cat="SBAR"><tok cat="IN">whether</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">supernatant</tok> <tok cat="NN">fluid</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">RCC</tok> <tok cat="NNS">explants</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">RCC-S</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">same</tok> <tok cat="NN">phenotype</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">suppression</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" id="i2" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">observed</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="RP">in</tok> <cons cat="NP"><tok cat="NN">patient</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1040217304@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">pattern</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">kappaB-binding</tok> <tok cat="NN">activity</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">RCC</tok> <tok cat="NN">patient</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">altered</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="SBAR"><tok cat="IN">as</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">compared</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">that</tok></cons> <cons cat="VP"><tok cat="VBN">seen</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="VP"><tok cat="VBN">obtained</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NNS">volunteers</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1040217305@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">some</tok> <tok cat="NNS">patients</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">no</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">RelA/NFkappaB1-binding</tok> <tok cat="NN">activity</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">detectable</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">others</tok></cons></cons> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="JJ">kappaB-binding</tok> <tok cat="NN">activity</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">modestly</tok></cons> <cons cat="VP"><tok cat="VBN">induced</tok> <cons cat="NP" ref="i4" null="NONE"></cons></cons></cons></cons><tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">duration</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">reduced</tok><cons cat="NP" ref="i5" null="NONE"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1040217306@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><tok cat="NN">IkappaBalpha</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">degraded</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">normally</tok></cons> <cons cat="PP" adv="TMP"><tok cat="VBG">following</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">stimulation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><tok cat="CC">both</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NNS">controls</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="NN">RCC</tok> <tok cat="NNS">patients</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1040217307@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NNS">RCC-S</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">alter</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">cytoplasmic</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">RelA</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">NF-kappaB1</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">did</tok> <cons cat="VP"><tok cat="VB">suppress</tok> <cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">localization</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">inhibited</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">RelA/NF-kappaB1</tok> <tok cat="NN">binding</tok> <tok cat="NNS">complexes</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1040217308@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">show</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NNS">RCC-S</tok></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">same</tok> <tok cat="NN">phenotype</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">impaired</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i7"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i7" id="i8" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">RCC</tok> <tok cat="NN">patient</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1040217309@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">It</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBZ">appears</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">suppression</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NNS">RCC-S</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">contribute</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">immunosuppression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">host</tok> <tok cat="NN">immunity</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1040327001@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">Monoclonal</tok> <tok cat="JJ">anti-endothelial</tok> <tok cat="NN">cell</tok> <tok cat="NNS">antibodies</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">patient</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Takayasu</tok> <tok cat="NN">arteritis</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBP">activate</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="JJ">large</tok> <tok cat="NNS">vessels</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1040327002@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">OBJECTIVE</tok><tok cat="COLON">:</tok></cons> <cons cat="S" syn="COOD"><cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">create</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">monoclonal</tok> <tok cat="JJ">anti-endothelial</tok> <tok cat="NN">cell</tok> <tok cat="NNS">antibodies</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">mAECA</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">patient</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Takayasu</tok> <tok cat="NN">arteritis</tok></cons></cons></cons></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">evaluate</tok> <cons cat="NP"><cons cat="NP"><tok cat="PRPP">their</tok> <tok cat="NN">ability</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">umbilical</tok> <tok cat="NN">vein</tok> <tok cat="JJ">endothelial</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">HUVEC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S" func="ADV"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">characterize</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">mechanism</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">EC</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@41@@oe@16-12-2010 1040327003@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NNS">METHODS</tok><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="NN">panel</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">mAECA</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">generated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">peripheral</tok> <tok cat="NN">blood</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">patient</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Takayasu</tok> <tok cat="NN">arteritis</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="JJ">Epstein-Barr</tok> <tok cat="NN">virus</tok> <tok cat="NN">transformation</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1040327004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="NN">Activity</tok></cons> <cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="JJ">macrovascular</tok> <tok cat="NN">EC</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">HUVEC</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">microvascular</tok> <tok cat="NN">EC</tok> <tok cat="LRB">(</tok><tok cat="JJ">human</tok> <tok cat="NN">bone</tok> <tok cat="NN">marrow</tok> <tok cat="NN">EC</tok> <tok cat="VBN">immortalized</tok> <tok cat="IN">by</tok> <tok cat="NN">SV40</tok><tok cat="RRB">)</tok> <tok cat="NNS">antigens</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">detected</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="JJ">enzyme-linked</tok> <tok cat="JJ">immunosorbent</tok> <tok cat="NN">assay</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1040327005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="NN">Inhibition</tok> <tok cat="NNS">studies</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">select</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="JJ">monoclonal</tok> <tok cat="NNS">antibodies</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NNS">mAECA</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">share</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">same</tok> <tok cat="NN">EC</tok> <tok cat="NN">epitope</tok> <tok cat="NN">binding</tok> <tok cat="NN">specificity</tok></cons> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">total</tok> <tok cat="NN">IgG-AECA</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">Takayasu</tok> <tok cat="NN">arteritis</tok> <tok cat="NN">patient</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1040327006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NNS">mAECA</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">aortic</tok> <tok cat="NN">EC</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">studied</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">immunohistochemistry</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1040327007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">secretion</tok> <tok cat="NNS">levels</tok></cons> <cons cat="S" ref="i7" null="ICH"></cons></cons><cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin-6</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-6</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">von</tok> <tok cat="NN">Willebrand</tok> <tok cat="NN">factor</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">vWF</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">determined</tok><cons cat="NP" ref="i6" null="NONE"></cons><tok cat="COMMA">,</tok> <cons cat="S" id="i7"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">serve</tok> <cons cat="PP"><tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">markers</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">EC</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@26@@oe@16-12-2010 1040327008@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i8" role="SBJ"><tok cat="DT">The</tok> <tok cat="VBN">activated</tok> <tok cat="NN">EC</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">examined</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">adherence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">monocytic</tok> <tok cat="NN">cell</tok> <tok cat="NN">line</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">U937</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="CONJP"><tok cat="RB">as</tok> <tok cat="RB">well</tok> <tok cat="IN">as</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">vascular</tok> <tok cat="NN">cell</tok> <tok cat="NN">adhesion</tok> <tok cat="NN">molecule</tok> <tok cat="CD">1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="JJ">intercellular</tok> <tok cat="NN">adhesion</tok> <tok cat="NN">molecule</tok> <tok cat="CD">1</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">E-selectin</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@37@@oe@16-12-2010 1040327009@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i9" role="SBJ"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NNS">extracts</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">mAECA-treated</tok> <tok cat="NN">EC</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">analyzed</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">induction</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">translocation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NN">factor</tok> <tok cat="NN">kappaB</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">specific</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">oligoprobe</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="JJ">electrophoretic</tok> <tok cat="NN">mobility</tok> <tok cat="NN">shift</tok> <tok cat="NN">assay</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@36@@oe@16-12-2010 1040327010@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NNS">RESULTS</tok><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" id="i10" role="SBJ"><tok cat="CD">Six</tok> <tok cat="NNS">mAECA</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">selected</tok><cons cat="NP" ref="i10" null="NONE"></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i11"><cons cat="WHNP"><tok cat="DT">the</tok> <tok cat="NN">mixture</tok></cons> <cons cat="WHPP"><tok cat="IN">of</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons></cons> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">produced</tok> <cons cat="NP"><cons cat="NP"><tok cat="CD">100</tok><tok cat="NN">%</tok> <tok cat="NN">inhibition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">binding</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">original</tok> <tok cat="NN">IgG</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">patient</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Takayasu</tok> <tok cat="NN">arteritis</tok></cons></cons></cons></cons><tok cat="RRB">)</tok></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NNS">HUVEC</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1040327011@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">All</tok> <tok cat="NNS">mAECA</tok></cons> <cons cat="VP"><tok cat="VBD">possessed</tok> <cons cat="NP"><tok cat="JJ">high</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">against</tok> <cons cat="NP"><tok cat="JJ">macrovascular</tok> <tok cat="NN">EC</tok></cons></cons></cons><tok cat="COMMA">,</tok></cons> <tok cat="CC">but</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">none</tok></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><tok cat="JJ">significant</tok> <tok cat="JJ">antimicrovascular</tok> <tok cat="NN">EC</tok> <tok cat="NN">activity</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1040327012@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><tok cat="DT">The</tok> <cons cat="NP"><tok cat="NNS">mAECA</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="JJ">human</tok> <tok cat="NN">IgG</tok></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="NP"><tok cat="JJ">anti-human</tok> <tok cat="JJ">aortic</tok> <tok cat="NN">EC</tok> <tok cat="NN">activity</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1040327013@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="CD">Four</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="CD">6</tok> <tok cat="NNS">mAECA</tok> <tok cat="VBD">activated</tok> <tok cat="NN">EC</tok></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="VBN">manifested</tok> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" syn="COOD" role="LGS"><tok cat="VBN">increased</tok> <cons cat="NP"><tok cat="NN">IL-6</tok> <cons cat="NP" ref="i12" null="RNR"></cons></cons><tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">vWF</tok> <cons cat="NP" ref="i12" null="RNR"></cons></cons><cons cat="NP" id="i12"><tok cat="NN">secretion</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1040327014@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="CD">4</tok> <tok cat="NNS">mAECA</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBD">induced</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">EC</tok> <tok cat="NN">expression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">adhesion</tok> <tok cat="NNS">molecules</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBD">increased</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">adhesion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">U937</tok> <tok cat="JJ">monocytic</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">EC</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1040327015@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">addition</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">these</tok> <tok cat="NNS">mAECA</tok></cons> <cons cat="VP"><tok cat="VBD">stimulated</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">nuclear</tok> <tok cat="NN">translocation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1040327016@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">CONCLUSION</tok><tok cat="COLON">:</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRPP">Our</tok> <tok cat="NNS">findings</tok></cons> <cons cat="VP"><tok cat="VBP">suggest</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NNS">AECA</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="MD">may</tok> <cons cat="ADVP"><tok cat="RB">directly</tok></cons> <cons cat="VP"><tok cat="VB">stimulate</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">EC</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">Takayasu</tok> <tok cat="NN">arteritis</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">elevation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">adhesion</tok> <tok cat="NN">molecule</tok> <tok cat="NN">expression</tok></cons> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">adhesion</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">monocytes</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="ADVP"><tok cat="RB">therefore</tok></cons> <cons cat="VP"><tok cat="VB">play</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">pathogenic</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">development</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">vasculopathy</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">Takayasu</tok> <tok cat="NN">arteritis</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@46@@oe@16-12-2010 1040377001@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><tok cat="NN">ICSAT</tok> <tok cat="NN">overexpression</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <tok cat="RB">not</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">sufficient</tok> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">cause</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">adult</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">leukemia</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">multiple</tok> <tok cat="NN">myeloma</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1040377002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">ICSAT</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">Interferon</tok> <tok cat="NN">Consensus</tok> <tok cat="NN">Sequence</tok> <tok cat="NN">binding</tok> <tok cat="NN">protein</tok> <tok cat="IN">for</tok> <tok cat="VBN">Activated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">lymphocyte-specific</tok> <tok cat="NN">member</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">interferon</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">factor</tok> <tok cat="LRB">(</tok><tok cat="NN">IRF</tok><tok cat="RRB">)</tok> <tok cat="NN">family</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">originally</tok></cons> <tok cat="VBN">identified</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Southwestern</tok> <tok cat="NN">screening</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">ATL</tok><tok cat="LRB">(</tok><tok cat="NN">Adult</tok> <tok cat="NN">T-cell</tok> <tok cat="NN">leukemia</tok><tok cat="RRB">)</tok><tok cat="JJ">-16T</tok> <tok cat="NN">expression</tok> <tok cat="NN">library</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@46@@oe@16-12-2010 1040377003@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">study</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">created</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">transgenic</tok> <tok cat="NNS">mice</tok></cons> <cons cat="VP"><tok cat="VBG">overexpressing</tok> <cons cat="NP"><tok cat="NN">ICSAT</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">lymphocytes</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@13@@oe@16-12-2010 1040377004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" func="ADV"><tok cat="IN">Although</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="JJ">spontaneous</tok> <tok cat="NN">tumorigenesis</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">observed</tok><cons cat="NP" ref="i2" null="NONE"></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i3" role="SBJ"><cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">Concanavalin</tok> <tok cat="NN">A</tok> <tok cat="NN">stimulation</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBN">increased</tok> <cons cat="NP" ref="i3" null="NONE"></cons><tok cat="IN">in</tok> <tok cat="JJ">transgenic</tok> <tok cat="NNS">mice</tok> <tok cat="VBG">overexpressing</tok> <tok cat="NN">ICSAT</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1040377005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">ICSAT</tok> <tok cat="NN">overexpression</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">lymphocytes</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">seems</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">insufficient</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">leukemogenesis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">ATL</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">multiple</tok> <tok cat="NN">myeloma</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MM</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="S" syn="COOD"><cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">it</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">regulate</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NN">cell</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP" role="SBJ"><tok cat="PRPP">its</tok> <tok cat="NN">overexpression</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">lead</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="NN">leukemogenesis</tok></cons></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">controlling</tok> <cons cat="NP"><tok cat="NN">IL-2</tok> <tok cat="NN">production</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@38@@oe@16-12-2010 1040377006@GENIA Treebank@formal@@1@S@<cons cat="NP"><tok cat="NN">Copyright</tok> <tok cat="CD">1999</tok> <tok cat="NNP">Academic</tok> <tok cat="NNP">Press</tok><tok cat="PERIOD">.</tok></cons>@@@@1@5@@oe@16-12-2010 1040758001@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="NN">Clonality</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">granulocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">healthy</tok> <tok cat="NNS">females</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">PCR-based</tok> <tok cat="NN">HUMARA</tok> <tok cat="NN">method</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@16@@oe@16-12-2010 1040758002@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="NN">Clonality</tok> <tok cat="NN">analysis</tok></cons> <cons cat="VP"><tok cat="VBG">utilizing</tok> <cons cat="NP"><tok cat="NN">X-chromosome</tok> <tok cat="NN">inactivation</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">used</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">study</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">various</tok> <tok cat="NNS">diseases</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP"><tok cat="JJ">hematological</tok> <tok cat="NNS">malignancies</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1040758003@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="JJ">human</tok> <tok cat="NN">androgen</tok> <tok cat="NN">receptor</tok> <tok cat="NN">gene</tok> <tok cat="LRB">(</tok><tok cat="NN">HUMARA</tok><tok cat="RRB">)</tok> <tok cat="NN">assay</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJS">newest</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">such</tok> <tok cat="NNS">methods</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <tok cat="CC">and</tok> <cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">majority</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">female</tok> <tok cat="NN">population</tok></cons></cons></cons> <cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">assessed</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="DT">this</tok> <cons cat="ADJP"><tok cat="RB">relatively</tok> <tok cat="JJ">simple</tok></cons> <tok cat="NN">procedure</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1040758004@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="CD">One</tok> <tok cat="NN">problem</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NN">clonality</tok> <tok cat="NN">analysis</tok> <tok cat="NNS">methods</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="SBAR" role="PRD"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="EX">there</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP"><tok cat="JJ">significant</tok> <tok cat="NN">variation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Lyonization</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">blood</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NNS">individuals</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1040758005@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S" func="ADV"><cons cat="NP" ref="i3" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">To</tok> <cons cat="VP"><tok cat="VB">determine</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">diversity</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">X-chromosome</tok> <tok cat="NN">methylation</tok> <tok cat="NNS">patterns</tok></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><cons cat="WHNP" id="i4"><tok cat="WDT">which</tok></cons> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBP">reflect</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">Lyonization</tok></cons><tok cat="COMMA">,</tok> <cons cat="VP"><tok cat="VBN">assessed</tok> <cons cat="NP" null="NONE"></cons><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">HUMARA</tok> <tok cat="NN">assay</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <cons cat="ADJP"><tok cat="RB">supposedly</tok> <tok cat="JJ">normal</tok></cons> <tok cat="NN">population</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i3" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">analyzed</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">granulocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="CD">97</tok> <cons cat="ADJP"><cons cat="ADJP"><tok cat="RB">relatively</tok> <tok cat="JJ">young</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="CD">18-</tok> <cons cat="ADJP" null="QSTN"></cons></cons><tok cat="TO">to</tok> <cons cat="ADJP"><tok cat="JJ">35-year-old</tok></cons></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="JJ">healthy</tok> <tok cat="JJ">female</tok> <tok cat="NNS">volunteers</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@43@@oe@16-12-2010 1040758006@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">methylation</tok> <tok cat="NNS">patterns</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="CD">two</tok> <tok cat="NN">HUMARA</tok> <tok cat="NNS">alleles</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">distributed</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="ADVP"><cons cat="ADVP"><cons cat="ADJP"><tok cat="RB">even</tok> <tok cat="RBR">more</tok></cons> <tok cat="RB">widely</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP" syn="COOD"><tok cat="CC">both</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">granuloctyes</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">than</tok> <cons cat="NP"><cons cat="NP"><tok cat="RB">previously</tok> <tok cat="VBN">reported</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">other</tok> <tok cat="NNS">methods</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@32@@oe@16-12-2010 1040758007@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">also</tok></cons> <cons cat="VP"><tok cat="VBD">found</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">deviation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">methylation</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NNS">granulocytes</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">well</tok></cons> <cons cat="VP"><tok cat="VBN">correlated</tok><cons cat="NP" ref="i6" null="NONE"></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1040758008@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Thus</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBP">conclude</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">appropriate</tok> <tok cat="NNS">controls</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">same</tok> <tok cat="NNS">individuals</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="JJ">such</tok> <tok cat="IN">as</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">case</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">stem</tok> <tok cat="NN">cell</tok> <tok cat="NNS">disorders</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="VP"><tok cat="MD">should</tok> <cons cat="ADVP"><tok cat="RB">always</tok></cons> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">employed</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="ADVP"><tok cat="RB">conclusively</tok></cons> <cons cat="VP"><tok cat="VB">determine</tok> <cons cat="SBAR"><tok cat="IN">whether</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="JJ">certain</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">hematopoietic</tok> <tok cat="NN">origin</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">clonal</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1040976301@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">The</tok> <tok cat="JJ">Epstein-Barr</tok> <tok cat="NN">virus</tok> <tok cat="NN">oncoprotein</tok> <tok cat="JJ">latent</tok> <tok cat="NN">membrane</tok> <tok cat="NN">protein</tok> <tok cat="CD">1</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">engages</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok> <tok cat="JJ">receptor-associated</tok> <tok cat="NNS">proteins</tok> <tok cat="NN">TRADD</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">receptor-interacting</tok> <tok cat="NN">protein</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">RIP</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <tok cat="CC">but</tok> <cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons></cons> <tok cat="CC">or</tok> <cons cat="VP"><tok cat="VB">require</tok> <cons cat="NP"><tok cat="NN">RIP</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@34@@oe@16-12-2010 1040976302@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="NN">site</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">Epstein-Barr</tok> <tok cat="NN">virus</tok> <tok cat="LRB">(</tok><tok cat="NN">EBV</tok><tok cat="RRB">)</tok> <tok cat="NN">transforming</tok> <tok cat="NN">protein</tok> <tok cat="NN">LMP1</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i1"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i1" role="SBJ" null="T"></cons><cons cat="ADVP"><tok cat="RB">constitutively</tok></cons> <cons cat="VP"><tok cat="VBZ">associates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok> <tok cat="NN">receptor</tok> <tok cat="CD">1</tok> <tok cat="LRB">(</tok><tok cat="NN">TNFR1</tok><tok cat="RRB">)</tok><tok cat="JJ">-associated</tok> <tok cat="NN">death</tok> <tok cat="NN">domain</tok> <tok cat="NN">protein</tok> <tok cat="NN">TRADD</tok></cons></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">mediate</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">c-Jun</tok> <tok cat="JJ">N-terminal</tok> <tok cat="NN">kinase</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">critical</tok> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="JJ">long-term</tok> <tok cat="JJ">lymphoblastoid</tok> <tok cat="NN">cell</tok> <tok cat="NN">proliferation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@46@@oe@16-12-2010 1040976303@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="ADVP"><tok cat="RB">now</tok></cons> <cons cat="VP"><tok cat="VBP">find</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">LMP1</tok> <tok cat="NN">signaling</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="NN">TRADD</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">differs</tok> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">TNFR1</tok> <tok cat="NN">signaling</tok></cons> <cons cat="PP"><tok cat="IN">through</tok> <cons cat="NP"><tok cat="NN">TRADD</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1040976304@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">LMP1</tok></cons> <cons cat="VP"><tok cat="VBZ">needs</tok> <cons cat="NP"><cons cat="QP"><tok cat="RB">only</tok> <tok cat="CD">11</tok></cons> <tok cat="NN">amino</tok> <tok cat="NNS">acids</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VB">activate</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok></cons></cons> <tok cat="CC">or</tok> <cons cat="VP"><tok cat="VB">synergize</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">TRADD</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">TNFR1</tok></cons> <cons cat="VP"><tok cat="VBZ">requires</tok> <cons cat="NP"><cons cat="QP"><tok cat="RB">approximately</tok> <tok cat="CD">70</tok></cons> <tok cat="NNS">residues</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1040976305@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Further</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">LMP1</tok></cons> <cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">require</tok> <cons cat="NP"><tok cat="NN">TRADD</tok> <tok cat="NNS">residues</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">294</tok></cons> <tok cat="TO">to</tok> <cons cat="NP"><tok cat="CD">312</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="SBAR"><tok cat="IN">while</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">TNFR1</tok></cons> <cons cat="VP"><tok cat="VBZ">requires</tok> <cons cat="NP"><tok cat="NN">TRADD</tok> <tok cat="NNS">residues</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">296</tok></cons> <tok cat="TO">to</tok> <cons cat="NP"><tok cat="CD">302</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1040976306@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><tok cat="NN">LMP1</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADVP"><tok cat="RB">partially</tok></cons> <cons cat="VP"><tok cat="VBN">blocked</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">TRADD</tok> <tok cat="NN">mutant</tok></cons> <cons cat="VP"><tok cat="VBG">consisting</tok> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">residues</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="CD">122</tok></cons> <tok cat="TO">to</tok> <cons cat="NP"><tok cat="CD">293</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1040976307@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Unlike</tok> <cons cat="NP"><tok cat="NN">TNFR1</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">LMP1</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="MD">can</tok> <cons cat="VP"><tok cat="VB">interact</tok> <cons cat="ADVP"><tok cat="RB">directly</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">receptor-interacting</tok> <tok cat="NN">protein</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">RIP</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><cons cat="ADVP"><tok cat="RB">stably</tok></cons> <tok cat="VBZ">associates</tok> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="NN">RIP</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">EBV-transformed</tok> <tok cat="JJ">lymphoblastoid</tok> <tok cat="NN">cell</tok> <tok cat="NNS">lines</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1040976308@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Surprisingly</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">LMP1</tok></cons> <cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">require</tok> <cons cat="NP"><tok cat="NN">RIP</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1040976309@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">Despite</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">constitutive</tok> <tok cat="NN">association</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">TRADD</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="NN">RIP</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">LMP1</tok></cons> <cons cat="VP"><tok cat="VBZ">does</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">induce</tok> <cons cat="NP"><tok cat="NN">apoptosis</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">EBV-negative</tok> <tok cat="NN">Burkitt</tok> <tok cat="NN">lymphoma</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">human</tok> <tok cat="JJ">embryonic</tok> <tok cat="NN">kidney</tok> <tok cat="CD">293</tok> <cons cat="NP" ref="i3" null="RNR"></cons></cons><cons cat="NP" id="i3"><tok cat="NNS">cells</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1040976310@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">results</tok></cons> <cons cat="VP"><tok cat="VBP">add</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">different</tok> <tok cat="NN">perspective</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">molecular</tok> <tok cat="NNS">interactions</tok></cons> <cons cat="SBAR"><cons cat="WHPP" id="i4"><tok cat="IN">through</tok> <cons cat="WHNP"><tok cat="WDT">which</tok></cons></cons> <cons cat="S"><cons cat="NP" syn="COOD" role="SBJ"><cons cat="NP"><tok cat="NN">LMP1</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><tok cat="NN">TRADD</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">RIP</tok></cons></cons> <cons cat="VP"><tok cat="VBP">participate</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">B-lymphocyte</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">activation</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">growth</tok></cons></cons></cons></cons><cons cat="PP" ref="i4" null="T"></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@25@@oe@16-12-2010 1041100301@GENIA Treebank@formal@@1@S@<cons cat="NP"><cons cat="NP"><tok cat="JJ">Regulatory</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">interleukin-11</tok></cons></cons> <cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><tok cat="JJ">acute</tok> <tok cat="NN">lung</tok> <tok cat="JJ">inflammatory</tok> <tok cat="NN">injury</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@10@@oe@16-12-2010 1041100302@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">interleukin-11</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">IL-11</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">evaluated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">IgG</tok> <tok cat="JJ">immune</tok> <tok cat="NN">complex</tok> <tok cat="NN">model</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">acute</tok> <tok cat="NN">lung</tok> <tok cat="NN">injury</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NNS">rats</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1041100303@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" syn="COOD" id="i2" role="SBJ"><cons cat="NP"><tok cat="NN">IL-11</tok> <tok cat="NN">mRNA</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">protein</tok></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="ADVP"><tok cat="DT">both</tok></cons> <cons cat="VP"><tok cat="VBN">up-regulated</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP" adv="TMP"><tok cat="IN">during</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">course</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="JJ">inflammatory</tok> <tok cat="NN">response</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1041100304@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="ADJP"><tok cat="RB">Exogenously</tok> <tok cat="VBN">administered</tok></cons> <tok cat="NN">IL-11</tok></cons> <cons cat="ADVP"><tok cat="RB">substantially</tok></cons> <cons cat="VP"><tok cat="VBD">reduced</tok><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">dose-dependent</tok> <tok cat="NN">manner</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">intrapulmonary</tok> <tok cat="NN">accumulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NNS">neutrophils</tok></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">lung</tok> <tok cat="JJ">vascular</tok> <tok cat="NN">leak</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">albumin</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1041100305@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="DT">These</tok> <cons cat="NP"><cons cat="ADJP"><tok cat="FW">in</tok> <tok cat="FW">vivo</tok></cons> <tok cat="JJ">anti-inflammatory</tok> <tok cat="NNS">effects</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-11</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="VBN">reduced</tok> <tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">lung</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBD">reduced</tok> <tok cat="NNS">levels</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok> <tok cat="NN">alpha</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons><tok cat="RRB">)</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">bronchoalveolar</tok> <tok cat="NN">lavage</tok> <tok cat="LRB">(</tok><tok cat="NN">BAL</tok><tok cat="RRB">)</tok> <tok cat="NNS">fluids</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBD">diminished</tok> <tok cat="NN">up-regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">lung</tok> <tok cat="JJ">vascular</tok> <tok cat="NN">ICAM-1</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@42@@oe@16-12-2010 1041100306@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">It</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">interesting</tok> <cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-11</tok></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">BAL</tok> <tok cat="JJ">fluid</tok> <tok cat="NN">content</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP" syn="COOD"><tok cat="DT">the</tok> <cons cat="NP"><tok cat="NN">CXC</tok> <tok cat="NNS">chemokines</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">macrophage</tok> <tok cat="JJ">inflammatory</tok> <tok cat="NN">protein-2</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">MIP-2</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">cytokine-inducible</tok> <tok cat="NN">neutrophil</tok> <tok cat="NN">chemoattractant</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">CINC</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COLON">;</tok></cons> <cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">presence</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">IL-11</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">did</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VB">affect</tok> <cons cat="NP"><tok cat="DT">these</tok> <tok cat="NNS">chemokines</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@40@@oe@16-12-2010 1041100307@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">However</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i4" role="SBJ"><cons cat="NP"><tok cat="NN">BAL</tok> <tok cat="NN">content</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">C5a</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">reduced</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><tok cat="NN">IL-11</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1041100308@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">These</tok> <tok cat="NNS">data</tok></cons> <cons cat="VP"><tok cat="VBP">indicate</tok> <cons cat="SBAR" syn="COOD"><cons cat="SBAR"><tok cat="IN">that</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">IL-11</tok></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="NP" role="PRD"><tok cat="DT">a</tok> <tok cat="JJ">regulatory</tok> <tok cat="NN">cytokine</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">lung</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="SBAR"><tok cat="IN">that</tok><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="PP"><tok cat="IN">like</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">other</tok> <tok cat="NNS">members</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">family</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><tok cat="PRPP">its</tok> <tok cat="JJ">anti-inflammatory</tok> <tok cat="NNS">properties</tok></cons> <cons cat="VP"><tok cat="VBP">appear</tok> <cons cat="S"><cons cat="NP" ref="i5" id="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="VP"><tok cat="VBN">linked</tok> <cons cat="NP" ref="i7" null="NONE"></cons><cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><cons cat="NP"><tok cat="PRPP">its</tok> <tok cat="NN">suppression</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappaB</tok> <tok cat="NN">activation</tok></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">diminished</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><cons cat="NP"><tok cat="VBN">reduced</tok> <tok cat="NN">up-regulation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">lung</tok> <tok cat="JJ">vascular</tok> <tok cat="NN">ICAM-1</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@49@@oe@16-12-2010 1041100701@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">ETS</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons> <cons cat="VP"><tok cat="VBP">regulate</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">enhancer</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">third</tok> <tok cat="NN">intron</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@14@@oe@16-12-2010 1041100702@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBP">describe</tok> <cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">enhancer</tok> <tok cat="NN">site</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">third</tok> <tok cat="NN">intron</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">tumor</tok> <tok cat="NN">necrosis</tok> <tok cat="NN">factor</tok> <tok cat="NN">alpha</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@18@@oe@16-12-2010 1041100703@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">A</tok> <tok cat="NN">reporter</tok> <tok cat="NN">construct</tok></cons> <cons cat="VP"><tok cat="VBG">containing</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">5'-flanking</tok> <tok cat="NN">region</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">mouse</tok> <tok cat="NN">TNF-alpha</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">displayed</tok> <cons cat="NP"><tok cat="JJ">weak</tok> <tok cat="NN">activity</tok></cons> <cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i1"><tok cat="WRB">when</tok></cons> <cons cat="S"><cons cat="NP" id="i2" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">transfected</tok> <cons cat="NP" null="NONE"></cons><cons cat="PP"><tok cat="IN">into</tok> <cons cat="NP"><tok cat="NN">RAW264.7</tok> <tok cat="JJ">macrophage-like</tok> <tok cat="NNS">cells</tok></cons></cons><cons cat="ADVP" ref="i1" null="T"></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@22@@oe@16-12-2010 1041100704@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="NN">addition</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">third</tok> <tok cat="NN">intron</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons></cons></cons></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">construct</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">resulted</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">an</tok> <tok cat="NN">enhancement</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">CAT</tok> <tok cat="NN">protein</tok></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@19@@oe@16-12-2010 1041100705@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i3" role="SBJ"><tok cat="DT">This</tok> <tok cat="NN">enhancement</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">eliminated</tok> <cons cat="NP" ref="i3" null="NONE"></cons><cons cat="SBAR" syn="COOD"><cons cat="SBAR" func="ADV"><tok cat="IN">if</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="DT">a</tok> <tok cat="VBN">conserved</tok> <tok cat="JJ">20-bp</tok> <tok cat="NN">sequence</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">removed</tok> <cons cat="NP" ref="i4" null="NONE"></cons><cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">intron</tok></cons></cons></cons></cons></cons></cons> <tok cat="CC">or</tok> <cons cat="SBAR" func="ADV"><tok cat="IN">if</tok> <cons cat="S"><cons cat="NP" id="i5" role="SBJ"><tok cat="DT">a</tok> <tok cat="JJ">dominant-negative</tok> <tok cat="JJ">ets-binding</tok> <tok cat="NN">factor</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">co-transfected</tok> <cons cat="NP" ref="i5" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">reporter</tok> <tok cat="NN">gene</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@27@@oe@16-12-2010 1041100706@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NNS">Mutations</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">this</tok> <tok cat="NN">site</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i6"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i6" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">destroyed</tok> <cons cat="NP"><tok cat="JJ">potential</tok> <tok cat="NN">ets</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok> <tok cat="NN">binding</tok> <tok cat="NNS">sites</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">had</tok> <cons cat="VP"><tok cat="VBN">reduced</tok> <cons cat="NP"><tok cat="JJ">transcriptional</tok> <tok cat="NN">activity</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@17@@oe@16-12-2010 1041100707@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i7" role="SBJ"><cons cat="NP"><tok cat="DT">The</tok> <tok cat="JJ">major</tok> <tok cat="NN">transcription</tok> <tok cat="NN">factor</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i8"><tok cat="WDT">that</tok></cons> <cons cat="S"><cons cat="NP" ref="i8" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">bound</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">oligonucleotide</tok></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">confirmed</tok> <cons cat="S"><cons cat="NP" ref="i7" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP" role="PRD"><tok cat="NN">GABP</tok></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP" role="LGS"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">supershift</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="NN">competition</tok></cons></cons> <tok cat="NN">analysis</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1041100708@GENIA Treebank@formal@@1@S@<cons cat="S" syn="COOD"><cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><tok cat="NN">RAW264.7</tok> <tok cat="NNS">cells</tok></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">the</tok> <tok cat="NN">binding</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">constitutive</tok></cons></cons><tok cat="COMMA">,</tok></cons> <cons cat="S"><cons cat="ADVP"><tok cat="RB">however</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">bone</tok> <tok cat="JJ">marrow-derived</tok> <tok cat="NNS">macrophages</tok></cons></cons> <cons cat="NP" id="i9" role="SBJ"><tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="S"><cons cat="NP" ref="i9" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="ADJP" role="PRD"><tok cat="NN">interferon-gamma</tok> <tok cat="JJ">inducible</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@24@@oe@16-12-2010 1041100709@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="DT">This</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">imply</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">for</tok> <cons cat="NP"><tok cat="NN">ets</tok> <tok cat="NN">transcription</tok> <tok cat="NNS">factors</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">production</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">TNF-alpha</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1041507501@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i1" role="SBJ"><cons cat="NP"><tok cat="JJ">Abnormal</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">T</tok> <tok cat="NNS">lymphocytes</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">systemic</tok> <tok cat="NN">lupus</tok> <tok cat="NN">erythematosus</tok></cons></cons></cons></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBZ">is</tok> <cons cat="VP"><tok cat="VBN">associated</tok> <cons cat="NP" ref="i1" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="VBN">decreased</tok> <tok cat="NN">p65-RelA</tok> <tok cat="NN">protein</tok> <tok cat="NN">expression</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@21@@oe@16-12-2010 1041507502@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i2" role="SBJ"><cons cat="NP"><cons cat="NP"><tok cat="JJ">Numerous</tok> <cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="JJ">cellular</tok></cons> <tok cat="CC">and</tok> <cons cat="ADJP"><tok cat="JJ">biochemical</tok></cons></cons> <tok cat="NNS">abnormalities</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">immune</tok> <tok cat="NN">regulation</tok></cons></cons></cons> <cons cat="PP" ref="i3" null="ICH"></cons></cons><cons cat="VP"><tok cat="VBP">have</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">described</tok> <cons cat="NP" ref="i2" null="NONE"></cons><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NNS">patients</tok></cons> <cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">systemic</tok> <tok cat="NN">lupus</tok> <tok cat="NN">erythematosus</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">SLE</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="PP" id="i3"><tok cat="VBG">including</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">surface</tok> <tok cat="NN">Ag</tok> <tok cat="JJ">receptor-initiated</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">events</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">lymphokine</tok> <tok cat="NN">production</tok></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@31@@oe@16-12-2010 1041507503@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" func="ADV"><tok cat="IN">Because</tok> <cons cat="S"><cons cat="NP" id="i4" role="SBJ"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok></cons> <cons cat="VP" syn="COOD"><cons cat="VP"><tok cat="VBZ">contributes</tok> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">transcription</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">numerous</tok> <tok cat="JJ">inflammatory</tok> <tok cat="NNS">genes</tok></cons></cons></cons></cons></cons> <tok cat="CC">and</tok> <cons cat="VP"><tok cat="VBZ">has</tok> <cons cat="VP"><tok cat="VBN">been</tok> <cons cat="VP"><tok cat="VBN">shown</tok> <cons cat="S"><cons cat="NP" ref="i4" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">be</tok> <cons cat="NP" role="PRD"><cons cat="NP"><tok cat="DT">a</tok> <tok cat="JJ">molecular</tok> <tok cat="NN">target</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">antiinflammatory</tok> <tok cat="NNS">drugs</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i5" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">sought</tok> <cons cat="S"><cons cat="NP" ref="i5" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">characterize</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="JJ">functional</tok> <tok cat="NN">role</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">protein</tok> <tok cat="NN">complex</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">lupus</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@42@@oe@16-12-2010 1041507504@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" id="i6" role="SBJ"><cons cat="NP"><tok cat="RB">Freshly</tok> <tok cat="VBN">isolated</tok> <tok cat="NN">T</tok> <tok cat="NNS">cells</tok></cons> <cons cat="PP"><tok cat="IN">from</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">lupus</tok> <tok cat="NNS">patients</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP"><cons cat="NP"><cons cat="NP"><tok cat="JJ">rheumatoid</tok> <tok cat="NN">arthritis</tok></cons> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">RA</tok></cons><tok cat="RRB">)</tok></cons></cons> <tok cat="NNS">patients</tok></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NNS">individuals</tok></cons></cons></cons></cons> <cons cat="VP"><tok cat="VBD">were</tok> <cons cat="VP"><tok cat="VBN">activated</tok> <cons cat="NP" ref="i6" null="NONE"></cons><cons cat="ADVP"><tok cat="RB">physiologically</tok></cons> <cons cat="PP"><tok cat="IN">via</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">TCR</tok></cons></cons> <cons cat="S" syn="COOD"><cons cat="S"><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">anti-CD3</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="JJ">anti-CD28</tok> <tok cat="NNS">Abs</tok></cons></cons></cons> <cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">assess</tok> <cons cat="NP"><tok cat="JJ">proximal</tok> <tok cat="NN">membrane</tok> <tok cat="NN">signaling</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">and</tok> <cons cat="S"><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="NN">PMA</tok></cons> <tok cat="CC">and</tok> <cons cat="NP"><tok cat="DT">a</tok> <tok cat="NN">calcium</tok> <tok cat="NN">ionophore</tok> <cons cat="PRN"><tok cat="LRB">(</tok><cons cat="NP"><tok cat="NN">A23187</tok></cons><tok cat="RRB">)</tok></cons></cons></cons></cons> <cons cat="NP" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="TO">to</tok> <cons cat="VP"><tok cat="VB">bypass</tok> <cons cat="NP"><tok cat="JJ">membrane-mediated</tok> <tok cat="NN">signaling</tok> <tok cat="NNS">events</tok></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@51@@oe@16-12-2010 1041507505@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="PRP">We</tok></cons> <cons cat="VP"><tok cat="VBD">measured</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NNS">extracts</tok></cons></cons></cons> <cons cat="PP"><tok cat="IN">by</tok> <cons cat="NP"><tok cat="NN">gel</tok> <tok cat="NN">shift</tok> <tok cat="NN">analysis</tok></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1041507506@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" adv="TMP"><cons cat="WHADVP" id="i7"><tok cat="WRB">When</tok></cons> <cons cat="S"><cons cat="NP" id="i8" role="SBJ" null="NONE"></cons><cons cat="VP"><tok cat="VBN">compared</tok> <cons cat="NP" ref="i8" null="NONE"></cons><cons cat="PP"><tok cat="IN">with</tok> <cons cat="NP"><tok cat="JJ">normal</tok> <tok cat="NNS">cells</tok></cons></cons><cons cat="ADVP" ref="i7" null="T"></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i9" role="SBJ"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">activation</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">activity</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">SLE</tok> <tok cat="NNS">patients</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADVP"><tok cat="RB">significantly</tok></cons> <cons cat="VP"><tok cat="VBN">decreased</tok> <cons cat="NP" ref="i9" null="NONE"></cons><cons cat="PP" syn="COOD"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">SLE</tok><cons cat="NP" ref="i10" null="RNR"></cons></cons></cons><tok cat="COMMA">,</tok> <tok cat="CC">but</tok> <tok cat="RB">not</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">RA</tok><cons cat="NP" ref="i10" null="RNR"></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i10"><tok cat="NNS">patients</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@28@@oe@16-12-2010 1041507507@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">binding</tok> <tok cat="NN">activity</tok></cons> <cons cat="VP"><tok cat="VBD">was</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">absent</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="JJ">several</tok> <tok cat="NN">SLE</tok> <tok cat="NNS">patients</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i11"><tok cat="WP">who</tok></cons> <cons cat="S"><cons cat="NP" ref="i11" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">were</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBG">receiving</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">any</tok> <tok cat="NN">medication</tok></cons><tok cat="COMMA">,</tok> <cons cat="PP"><tok cat="VBG">including</tok> <cons cat="NP"><tok cat="NNS">corticosteroids</tok></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@20@@oe@16-12-2010 1041507508@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Also</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">activity</tok></cons> <cons cat="VP"><tok cat="VBD">remained</tok> <cons cat="ADJP" role="PRD"><tok cat="JJ">absent</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="JJ">follow-up</tok> <tok cat="NNS">studies</tok></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@11@@oe@16-12-2010 1041507509@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="PP"><tok cat="IN">In</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">supershift</tok> <tok cat="NNS">experiments</tok></cons> <cons cat="VP"><tok cat="VBG">using</tok> <cons cat="NP"><tok cat="JJ">specific</tok> <tok cat="NNS">Abs</tok></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="PRP">we</tok></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="SBAR"><tok cat="IN">that</tok><tok cat="COMMA">,</tok> <cons cat="S"><cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">group</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">SLE</tok> <tok cat="NNS">patients</tok></cons> <cons cat="SBAR"><cons cat="WHNP" id="i12"><tok cat="WP">who</tok></cons> <cons cat="S"><cons cat="NP" ref="i12" role="SBJ" null="T"></cons><cons cat="VP"><tok cat="VBD">displayed</tok> <cons cat="NP"><tok cat="JJ">undetectable</tok> <tok cat="NN">NF-kappa</tok> <tok cat="NN">B</tok> <tok cat="NN">activity</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" id="i13" role="SBJ"><tok cat="NN">p65</tok> <tok cat="NNS">complexes</tok></cons> <cons cat="VP"><tok cat="VBD">were</tok> <tok cat="RB">not</tok> <cons cat="VP"><tok cat="VBN">formed</tok><cons cat="NP" ref="i13" null="NONE"></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@30@@oe@16-12-2010 1041507510@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="ADVP"><tok cat="RB">Finally</tok></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><cons cat="NP"><tok cat="NN">immunoblot</tok> <tok cat="NN">analysis</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><tok cat="JJ">nuclear</tok> <tok cat="NNS">extracts</tok></cons></cons></cons> <cons cat="VP"><tok cat="VBD">showed</tok> <cons cat="NP"><cons cat="ADJP" syn="COOD"><cons cat="ADJP"><tok cat="VBN">decreased</tok></cons> <tok cat="CC">or</tok> <cons cat="ADJP"><tok cat="JJ">absent</tok></cons></cons> <tok cat="NN">p65</tok> <tok cat="NN">protein</tok> <tok cat="NNS">levels</tok></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@15@@oe@16-12-2010 1041507511@GENIA Treebank@formal@@1@S@<cons cat="S"><cons cat="SBAR" func="ADV"><tok cat="IN">As</tok> <cons cat="S"><cons cat="NP" role="SBJ"><tok cat="NN">p65</tok> <tok cat="NNS">complexes</tok></cons> <cons cat="VP"><tok cat="VBP">are</tok> <cons cat="ADJP"><tok cat="RB">transcriptionally</tok> <tok cat="JJ">active</tok> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><cons cat="NP"><tok cat="NN">comparison</tok></cons> <cons cat="PP"><tok cat="TO">to</tok> <cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">p50</tok> <tok cat="NN">homodimer</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="COMMA">,</tok> <cons cat="NP" role="SBJ"><tok cat="DT">this</tok> <tok cat="JJ">novel</tok> <tok cat="NN">finding</tok></cons> <cons cat="VP"><tok cat="MD">may</tok> <cons cat="VP"><tok cat="VB">provide</tok> <cons cat="NP"><tok cat="NN">insight</tok></cons> <cons cat="PP"><tok cat="IN">on</tok> <cons cat="NP"><cons cat="NP"><tok cat="DT">the</tok> <tok cat="NN">origin</tok></cons> <cons cat="PP"><tok cat="IN">of</tok> <cons cat="NP"><cons cat="NP" syn="COOD"><cons cat="NP"><tok cat="JJ">abnormal</tok> <tok cat="NN">cytokine</tok></cons> <tok cat="CC">or</tok> <cons cat="NP"><tok cat="JJ">other</tok> <tok cat="NN">gene</tok> <tok cat="NN">transcription</tok></cons></cons> <cons cat="PP"><tok cat="IN">in</tok> <cons cat="NP"><tok cat="NN">SLE</tok> <tok cat="NNS">patients</tok></cons></cons></cons></cons></cons></cons></cons></cons><tok cat="PERIOD">.</tok></cons>@@@@1@33@@oe@16-12-2010